The Role of the Immune System on the Cardiac Complications Observed in SARS-CoV-2

Abstract An acute respiratory syndrome caused by SARS-CoV2 was declared a pandemic by the World Health Organization. Current data in the world and in Brazil show that approximately 40% of patients who died have some type of cardiac comorbidity. There are also robust reports showing an increase in IL-6 / IL-1B / TNF-alpha and the presence of lymphopenia in patients with COVID-19. Our team and others have shown that increased cytokines are the link between arrhythmias/Left ventricular dysfunction and the immune system in different diseases. In addition, it has been well demonstrated that lymphopenia can not only be a good marker, but also a factor that causes heart failure. Thus, the present review focused on the role of the immune system upon the cardiac alterations observed in the SARS-CoV2 infection. Additionally, it was well described that SARS-CoV-2 is able to infect cardiac cells. Therefore, here it will be reviewed in deep.

Interaction of COVID-19 With Common Cardiovascular Disorders.

The onset and widespread dissemination of the severe acute respiratory syndrome coronavirus-2 in late 2019 impacted the world in a way not seen since the 1918 H1N1 pandemic, colloquially known as the Spanish Flu. Much like the Spanish Flu, which was observed to disproportionately impact young adults, it became clear in the early days of the coronavirus disease 2019 (COVID-19) pandemic that certain groups appeared to be at higher risk for severe illness once infected. One such group that immediately came to the forefront and garnered international attention was patients with preexisting cardiovascular disease. Here, we examine the available literature describing the interaction of COVID-19 with a myriad of cardiovascular conditions and diseases, paying particular attention to patients diagnosed with arrythmias, heart failure, and coronary artery disease. We further discuss the association of acute COVID-19 with de novo cardiovascular disease, including myocardial infarction due to coronary thrombosis, myocarditis, and new onset arrhythmias. We will evaluate various biochemical theories to explain these findings, including possible mechanisms of direct myocardial injury caused by the severe acute respiratory syndrome coronavirus-2 virus at the cellular level. Finally, we will discuss the strategies employed by numerous groups and governing bodies within the cardiovascular disease community to address the unprecedented challenges posed to the care of our most vulnerable patients, including heart transplant recipients, end-stage heart failure patients, and patients suffering from acute coronary syndromes, during the early days and height of the COVID-19 pandemic.

Furosemide-induced haemolytic anaemia in an extreme elderly patient.

Furosemide, a loop diuretic, is commonly used to treat fluid overload symptoms and heart failure. Drug-induced immune haemolytic anaemia is an unusual drug-adverse event. Furosemide-induced haemolysis is even rarer. This case report presents a 91-year-old male who developed acute haemolytic anaemia 3 days after initiating furosemide to treat myocardial infarction complicated with acute decompensated heart failure. He had increased lactate dehydrogenase and unconjugated bilirubin with undetectable haptoglobin, which indicated the destruction of red blood cells. Other causes for haemolytic anaemia, including hereditary, microangiopathic haemolytic anaemia, and paroxysmal nocturnal haemoglobinuria, were also excluded. He improved with drug cessation and a short course of glucocorticoids. This report aims to raise awareness of this rare complication caused by commonly prescribed drugs. Despite a negative result of a direct antiglobulin test, physicians must remain suspicious of drug-induced immune haemolytic anaemia in unclear cases of haemolysis.

Intravenous iron in patients with heart failure and iron deficiency: an updated meta-analysis.

AIMS: For patients with heart failure (HF) and iron deficiency (ID), randomized trials suggest that intravenous (IV) iron reduces hospitalizations for heart failure (HHF), but uncertainty exists about the effects in subgroups and the impact on mortality. We conducted a meta-analysis of randomized trials investigating the effect of IV iron on clinical outcomes in patients with HF. METHODS AND RESULTS: We identified randomized trials published between 1 January 2000 and 5 November 2022 investigating the effect of IV iron versus standard care/placebo in patients with HF and ID in any clinical setting, regardless of HF phenotype. Trials of oral iron or not in English were not included. The main outcomes of interest were a composite of HHF and cardiovascular death (CVD), on HHF alone and on cardiovascular and all-cause mortality. Ten trials were identified with 3373 participants, of whom 1759 were assigned to IV iron. IV iron reduced the composite of recurrent HHF and CVD (rate ratio 0.75, 95% confidence interval [CI] 0.61-0.93; p < 0.01) and first HHF or CVD (odds ratio [OR] 0.72, 95% CI 0.53-0.99; p = 0.04). Effects on cardiovascular (OR 0.86, 95% CI 0.70-1.05; p = 0.14) and all-cause mortality (OR 0.93, 95% CI 0.78-1.12; p = 0.47) were inconclusive. Results were similar in analyses confined to the first year of follow-up, which was less disrupted by the COVID-19 pandemic. Subgroup analyses found little evidence of heterogeneity for the effect on the primary endpoint, although patients with transferrin saturation <20% (OR 0.67, 95% CI 0.49-0.92) may have benefited more than those with values ≥20% (OR 0.99, 95% CI 0.74-1.30) (heterogeneity p = 0.07). CONCLUSION: In patients with HF and ID, this meta-analysis suggests that IV iron reduces the risk of HHF but whether this is associated with a reduction in cardiovascular or all-cause mortality remains inconclusive.

Effect of protein underdosing on the prognosis of patients with severe acute heart failure in the early acute phase: A single-institutional retrospective cohort study.

BACKGROUND: The appropriate protein dose during the early acute phase of severe acute heart failure (AHF) remains unknown. We hypothesized that protein underdosing during this period may lead to a poor prognosis. Thus, we investigated the relationship between protein sufficiency rate and prognosis during the early acute phase in patients with severe AHF. METHODS: This retrospective observational study investigated patients with AHF requiring invasive mechanical ventilation who were admitted in the intensive care and cardiac care units between January 2015 and August 2021. These patients were ranked according to the tertile of protein sufficiency rate on intubation day 2. Univariate and multivariate logistic regression analyses were performed to determine whether a low protein sufficiency rate on intubation day 2 was an independent factor for in-hospital mortality. Patients were weighted using the inverse probability of treatment weighting (IPTW) method to determine the differences in baseline characteristics. RESULTS: A total of 118 patients were included in the study and divided into low-protein (n = 40) and non-low-protein (n = 78) groups with protein sufficiency rates of ≤10% and >10%, respectively.In the multivariate analysis of in-hospital mortality, low protein sufficiency on day 2 was identified as an independent factor (odds ratio [OR] = 2.77, 95% confidence interval [CI] = 1.05-7.27, P = 0.039). After adjusting for baseline characteristics using the IPTW method, multiple logistic regression analysis of in-hospital mortality revealed low protein sufficiency on day 2 as an independent factor (OR = 3.32, 95% CI = 1.18-9.32, P = 0.023). CONCLUSION: Protein underdosing in the early acute phase of severe AHF may be associated with increased in-hospital mortality.

Impact of heart failure on all-cause mortality in COVID-19: findings from the Eurasian International Registry.

AIMS: To study all-cause mortality in patients hospitalized with COVID-19 with or without chronic heart failure (CHF) during hospitalization and at 3 and 6 months of follow-up. METHODS AND RESULTS: The international registry Analysis of Comorbid Disease Dynamics in Patients with SARS-CoV-2 Infection (ACTIV) was conducted at 26 centres in seven countries: Armenia, Belarus, Kazakhstan, Kyrgyzstan, Moldova, Russian Federation, and Uzbekistan. The primary endpoints were in-hospital all-cause mortality and all-cause mortality at 3 and 6 months of follow-up. Of the 5616 patients hospitalized with COVID-19, 917 (16.3%) had CHF. Total in-hospital mortality was 7.6%. In-hospital mortality was higher in patients with CHF than in patients without a history of CHF [17.7% vs. 4.0%, P < 0.001; odds ratio (OR) 4.614, 95% confidence interval (CI) 3.633-5.859; P < 0.001]. The risk of in-hospital all-cause mortality correlated significantly with the severity of CHF; specifically, the risk of in-hospital all-cause mortality was greater for patients in New York Heart Association functional classes III and IV (OR 6.124, 95% CI 4.538-8.266; P < 0.001 vs. patients without CHF) than for patients in functional classes I and II (OR 2.446, 95% CI 1.831-3.267, P < 0.001 vs. patients without CHF). The risk of mortality in patients with ischemic CHF was 58% higher than in patients with non-ischaemic CHF [OR 1.58 (95% CI 1.05-2.45), P = 0.030]. In the first 3 months of follow-up, the all-cause mortality rate in patients with CHF was 10.32%, compared with 1.83% in patients without CHF (P < 0.001). At 6 months of follow-up, NYHA classes II-IV was a strong risk factor for all-cause mortality [OR 5.343 (95% CI 2.717-10.508); P < 0.001]. CONCLUSIONS: Hospitalized COVID-19 patients with CHF have an increased risk of in-hospital all-cause mortality, which remains high 6 months after discharge.

Sigma-1 Receptor Signaling: In Search of New Therapeutic Alternatives for Cardiovascular and Renal Diseases.

Cardiovascular and renal diseases are among the leading causes of death worldwide, and regardless of current efforts, there is a demanding need for therapeutic alternatives to reduce their progression to advanced stages. The stress caused by diseases leads to the activation of protective mechanisms in the cell, including chaperone proteins. The Sigma-1 receptor (Sig-1R) is a ligand-operated chaperone protein that modulates signal transduction during cellular stress processes. Sig-1R interacts with various ligands and proteins to elicit distinct cellular responses, thus, making it a potential target for pharmacological modulation. Furthermore, Sig-1R ligands activate signaling pathways that promote cardioprotection, ameliorate ischemic injury, and drive myofibroblast activation and fibrosis. The role of Sig-1R in diseases has also made it a point of interest in developing clinical trials for pain, neurodegeneration, ischemic stroke, depression in patients with heart failure, and COVID-19. Sig-1R ligands in preclinical models have significantly beneficial effects associated with improved cardiac function, ventricular remodeling, hypertrophy reduction, and, in the kidney, reduced ischemic damage. These basic discoveries could inform clinical trials for heart failure (HF), myocardial hypertrophy, acute kidney injury (AKI), and chronic kidney disease (CKD). Here, we review Sig-1R signaling pathways and the evidence of Sig-1R modulation in preclinical cardiac and renal injury models to support the potential therapeutic use of Sig-1R agonists and antagonists in these diseases.

Effects of Body Mass Index on Presentation and Outcomes of COVID-19 among Heart Transplant and Left Ventricular Assist Device Patients: A Multi-Institutional Study.

The coronavirus disease 2019 (COVID-19) pandemic continues to pose a significant threat to patients receiving advanced heart failure therapies. The current study was undertaken to better understand the relationship between obesity and outcomes of SARS-CoV-2 infection in patients with a left ventricular assist device (LVAD) or heart transplant. We performed a retrospective review of patients with a heart transplant or LVAD who presented to one of the participating 11 institutions between April 1 and November 30, 2020. Patients were grouped by body mass index (BMI) into obese (BMI ≥ 30 k/m2) and nonobese cohorts (BMI < 30 kg/m2). Multivariable logistic regression models were used to estimate effects of obesity on outcomes of interest. Across all centers, 162 heart transplant and 81 LVAD patients were identified; 54 (33%) and 38 (47%) were obese, respectively. Obese patients tended to have more symptoms at presentation. No differences in rates of hospitalization or ICU admission were noted. Obese patients with LVADs were more likely to require mechanical ventilation (39% vs. 8%, p < 0.05). No differences in renal failure or secondary infection were noted. Mortality was similar among heart transplant patients (11% [obese] vs. 16% [nonobese], p = 0.628) and LVAD patients (12% vs. 15%, p = 1.0). BMI was not associated with increased adjusted odds of mortality, ICU admission, or mechanical ventilation (all p > 0.10). In summary, acute presentations of SARS-CoV-2 among heart transplant and LVAD recipients carry a significantly higher mortality than the general population, although BMI does not appear to impact this. Further studies on the longer-term effects of COVID-19 on this population are warranted.

The Utility of Home Sleep Apnea Testing in the Advanced Heart Failure Populations.

Untreated sleep disorders form a risk of coronary artery disease, hypertension, obesity, and diabetes mellitus. Access to polysomnography is limited, especially during the COVID-19 pandemic, with home sleep apnea testing (HSAT) being a potentially viable alternative. We describe an HSAT protocol in patients with advanced heart failure (HF). In a single-center, observational analysis between 2019 and 2021 in patients with advanced HF and heart transplant (HT), 135 screened positive on the STOP-Bang sleep survey and underwent a validated HSAT (WatchPAT, ZOLL-Itamar). HSAT was successful in 123 patients (97.6%), of whom 112 (91.1%; 84 HF and 28 HT) tested positive for sleep apnea. A total of 91% of sleep apnea cases were obstructive, and 63% were moderate to severe. Multivariable linear regression showed that the apnea hypopnea index was 34% lower in the HT group than in the HF group (p = 0.046) after adjusting for gender, and that this effect persisted in White patients but not among African-Americans. Patient characteristics were similar between groups, with coronary artery disease, diabetes mellitus, and hypertension as the most prevalent co-morbidities. In conclusion, sleep apnea remains prevalent in patients with HF with a high co-morbidity burden. HSAT is a feasible and effective tool for screening and diagnosis in this population.

Comorbidities associated with risk of ICU admission in elderly patients with COVID-19: Data from academic hospital in Saudi Arabia.

The coronavirus disease 2019 (COVID-19) has affected millions of people worldwide, of which 5% required intensive care, especially mechanical ventilation. The prognosis depends on several factors including comorbidities. This study was conducted to identify the comorbidities associated with the intensive care unit (ICU) admission in elderly with COVID-19 admitted to a tertiary academic hospital. A retrospective cross-sectional study was conducted at KSUMC including all hospitalized patients (age ≥ 65 years) with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection admitted between March 2020 and August 2021. Data collection included sociodemographic characteristics, underlying comorbidities, and the Charlson comorbidity index. Comorbidities were compared between the elderly patients with COVID-19 admitted to the ICU and those not admitted to the ICU. The odds ratios were calculated and a P value of < .05 and 95% confidence intervals were used to report the statistical significance A total of 444 patients (ICU = 147, non-ICU = 297) were included in the study. The study revealed that elderly patients with COVID-19 admitted to ICU had a higher rate of mortality (n = 64, 67.4%; P < .0001) and a higher proportion of them had shortness of breath (n = 97, 38.3%; P = .007) compared to the elderly patients not admitted to ICU. The mean length of stay (P < .0001), and weight (P = .02) among ICU patients were higher than the values for the non-ICU group, while the mean oxygen saturation (SpO2; P = .006) was lower among the ICU group. The comorbidities that demonstrated a statistically significant association with ICU admission were heart failure (P = .004, odd ratio (OR) = 2.02, 95% confidence intervals (CI) [1.263, 3540]), chronic obstructive pulmonary disease (COPD; P = .027, OR = 3.361, 95% CI [1.080, 10.464]), and chronic kidney disease (P = .021, OR = 1.807, 95% CI [1.087, 3.006]). The current study identified that the comorbidities such as COPD, heart failure, and factors like SpO2 and length of stay are associated with an increased risk of ICU admission in elderly patients with COVID-19. These findings highlight the clinical implications of comorbidity among geriatric population.

Cardiac function in critically ill patients with severe COVID: A prospective cross-sectional study in mechanically ventilated patients.

PURPOSE: To evaluate cardiac function in mechanically ventilated patients with COVID-19. MATERIALS AND METHODS: Prospective, cross-sectional multicenter study in four university-affiliated hospitals in Chile. All consecutive patients with COVID-19 ARDS requiring mechanical ventilation admitted between April and July 2020 were included. We performed systematic transthoracic echocardiography assessing right and left ventricular function within 24 h of intubation. RESULTS: 140 patients aged 57 ± 11, 29% female were included. Cardiac output was 5.1 L/min [IQR 4.5-6.2] and 86% of the patients required norepinephrine. ICU mortality was 29% (40 patients). Fifty-four patients (39%) exhibited right ventricle dilation out of whom 20 patients (14%) exhibited acute cor pulmonale (ACP). Eight out of the twenty patients with ACP exhibited pulmonary embolism (40%). Thirteen patients (9%) exhibited left ventricular systolic dysfunction (ejection fraction <45%). In the multivariate analysis acute cor pulmonale and PaO2/FiO2 ratio were independent predictors of ICU mortality. CONCLUSIONS: Right ventricular dilation is highly prevalent in mechanically ventilated patients with COVID-19 ARDS. Acute cor pulmonale was associated with reduced pulmonary function and, in only 40% of patients, with co-existing pulmonary embolism. Acute cor pulmonale is an independent risk factor for ICU mortality.

Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death among patients with chronic heart failure and a left ventricular ejection fraction of 40% or less. Whether SGLT2 inhibitors are effective in patients with a higher left ventricular ejection fraction remains less certain. METHODS: We randomly assigned 6263 patients with heart failure and a left ventricular ejection fraction of more than 40% to receive dapagliflozin (at a dose of 10 mg once daily) or matching placebo, in addition to usual therapy. The primary outcome was a composite of worsening heart failure (which was defined as either an unplanned hospitalization for heart failure or an urgent visit for heart failure) or cardiovascular death, as assessed in a time-to-event analysis. RESULTS: Over a median of 2.3 years, the primary outcome occurred in 512 of 3131 patients (16.4%) in the dapagliflozin group and in 610 of 3132 patients (19.5%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.92; P<0.001). Worsening heart failure occurred in 368 patients (11.8%) in the dapagliflozin group and in 455 patients (14.5%) in the placebo group (hazard ratio, 0.79; 95% CI, 0.69 to 0.91); cardiovascular death occurred in 231 patients (7.4%) and 261 patients (8.3%), respectively (hazard ratio, 0.88; 95% CI, 0.74 to 1.05). Total events and symptom burden were lower in the dapagliflozin group than in the placebo group. Results were similar among patients with a left ventricular ejection fraction of 60% or more and those with a left ventricular ejection fraction of less than 60%, and results were similar in prespecified subgroups, including patients with or without diabetes. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure and a mildly reduced or preserved ejection fraction. (Funded by AstraZeneca; DELIVER ClinicalTrials.gov number, NCT03619213.).

The Impact of COVID-19 on Family Caregivers of Individuals With End-Stage Heart Failure.

Before the COVID-19 pandemic, family caregivers were providing a tremendous amount of care for family members with heart failure with the prevalence of caregiver reliance in heart failure expected to increase in the United States. Social distancing and other restrictions during the COVID-19 pandemic may have added further challenges to caregiving routines. The purpose of this study was to examine the family caregiver perception of the effect of COVID-19 on caregiving routines. To determine caregiver perception of COVID-19's impact, 1 Likert question and 1 open-ended response were asked. Braun and Clark's method guided open-ended response thematic analysis. The 113 replies to the open-response question yielded themes such as social isolation, added fear, anxiety, or worry, changed appointments, wearing masks, and living status change. Social isolation (41.6%) was the most common theme; the most significant theme was living status change ( P = .003), and family caregivers reported that the pandemic affected their routines either negatively or somewhat negatively (62.1%). Family caregivers are affected during times of crisis. Research and policies that recognize the residual effects of COVID-19 on caregiving practices and support care transitions for family caregivers in the heart failure population are needed.

Elucidating the Role of Cardiac Biomarkers in COVID-19: A Narrative Evaluation with Clinical Standpoints and a Pragmatic Approach for Therapeutics.

With the incidence of the unabated spreading of the COVID-19 (coronavirus disease 2019) pandemic with an increase in heart-related complications in COVID-19 patients, laboratory investigations on general health and diseases of heart have greater importance. The production of a higher level of clots in the blood in COVID-19 individuals carries a high risk of severe lethal pneumonia, pulmonary embolism, or widespread thromboembolism. The COVID-19 pandemic has raised awareness regarding the severe consequences for the cardiac system that might cause due to severe acute respiratory distress syndrome (SARS-CoV-2). COVID-19 causes acute respiratory distress syndrome (ARDS), acute myocardial infarction, venous thromboembolism, and acute heart failure in people with preexisting cardiac illness. However, as COVID-19 is primarily a respiratory infectious disease, there is still a lot of debate on whether and how cardiac biomarkers should be used in COVID-19 patients. Considering the most practical elucidation of cardiac biomarkers in COVID-19, it is important to note that recent findings on the prognostic role of cardiac biomarkers in COVID-19 patients are similar to those found in pneumonia and ARDS studies. The use of natriuretic peptides and cardiac troponin concentrations as quantitative variables should help with COVID-19/pneumonia risk classification and ensure that these biomarkers sustain their high diagnostic precision for acute myocardial infarction and heart failure. Serial assessment of D-dimers will possibly aid clinicians in the assortment of patients for venous thromboembolism imaging in addition to the increase of anticoagulation from preventive to marginally higher or even therapeutic dosages because of the central involvement of endothelitis and thromboembolism in COVID-19. Therefore, cardiac biomarkers are produced in this phase because of some pathological processes; this review will focus on major cardiac biomarkers and their significant role in COVID-19.

Empagliflozin reduces markers of acute kidney injury in patients with acute decompensated heart failure.

AIMS: In this prospective, placebo-controlled, double-blind, exploratory study, we examined early and more delayed effects of empagliflozin treatment on haemodynamic parameters (primary endpoint: cardiac output) and kidney function including parameters of acute kidney injury (AKI) in patients with acute decompensated heart failure (HF). METHODS AND RESULTS: Patients with acute decompensated HF with or without diabetes were randomized to empagliflozin 10 mg or placebo for 30 days. Haemodynamic, laboratory, and urinary parameters were assessed after 6 h, 1 day, 3 days, 7 days, and 30 days of treatment. Median time between hospital admission and randomization was 72 h. Baseline characteristics were not different in the empagliflozin (n = 10) and placebo (n = 9) groups. Empagliflozin led to a significant increase in urinary glucose excretion throughout the study (baseline: 37 ± 15 mg/24 h; Day 1: 14 565 ± 8663 mg/24 h; P = 0.001). Empagliflozin did not affect the primary endpoint of cardiac index or on systemic vascular resistance index at any time point. However, empagliflozin significantly reduced parameters of AKI (urinary TIMP-2 and IGFBP7 by NephroCheck® as indicators of tubular kidney damage), which became significant after 3 days of treatment [placebo: 1.1 ± 1.1 (ng/mL)2 /1000; empagliflozin: 0.3 ± 0.2 (ng/mL)2 /1000; P = 0.02] and remained significant at the 7 day time point [placebo: 2.5 ± 3.8 (ng/mL)2 /1000; empagliflozin: 0.3 ± 0.2 (ng/mL)2 /1000; P = 0.003]. CONCLUSIONS: In this study, empagliflozin treatment did not affect haemodynamic parameters but significantly reduced markers of tubular injury in patients with acute decompensated HF.

Heart failure caused by Takayasu's arteritis in the time of COVID-19: a case report.

The case of a 35-year-old female with heart failure is presented, where the symptoms overlap with the heterogeneous manifestations of coronavirus disease 2019 (COVID-19). Those similarities and a recent shift in priorities during the SARS-CoV-2 pandemic delayed the recognition of acute heart failure in this patient. During the differential diagnostic process, obliterative disease was discovered in the bilateral subclavian and right renal arteries, and the latter resulted in uncontrolled hypertension, which played a significant role in the development of heart failure. The aetiology of vascular alterations turned out to be Takayasu's arteritis. Diagnosing Takayasu's arteritis is typically not straightforward due to its nonspecific signs and symptoms. Therefore, it can be concluded from our case report that the rising incidence of COVID-19 and focus on ruling out infection can potentially defer alternative, but appropriate diagnostic tests, particularly for certain conditions like rare diseases. Early identification and intervention is especially important for treating acute heart failure, whereas delay increases the risk of severe complications and mortality.

Changes in Acute Myocardial Infarction, Stroke, and Heart Failure Hospitalizations During COVID-19 Pandemic in Tuscany-An Interrupted Time Series Study.

Objectives: We evaluate the impact of the COVID-19 pandemic on unplanned hospitalization rates for patients without COVID-19, including their length of stay, and in-hospital mortality, overall, and for acute myocardial infarction (AMI), stroke, and heart failure in the Tuscany region of Italy. Methods: We carried out a population-based controlled interrupted time series study using segmented linear regression with an autoregressive error term based on admissions data from all public hospitals in Tuscany. The primary outcome measure was weekly hospitalization rates; secondary outcomes included length of stay, and in-hospital mortality. Results: The implementation of the pandemic-related mitigation measures and fear of infection was associated with large decreases in inpatient hospitalization rates overall (-182 [-234, -130]), unplanned hospitalization (-39 [-51, -26]), and for AMI (-1.32 [-1.98, -0.66]), stroke (-1.51 [-2.56, -0.44]), and heart failure (-8.7 [-11.1, -6.3]). Average length of stay and percent in-hospital mortality for select acute medical conditions did not change significantly. Conclusion: In Tuscany, Italy, the COVID-19 pandemic was associated with large reductions in hospitalization rates overall, as well as for heart failure, and the time sensitive conditions of AMI and stroke during the months January to July 2020.