Heart Rate Variability in Subjects with Severe Allergic Background Undergoing COVID-19 Vaccination.

Anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination is the world's most important strategy for stopping the pandemic. Vaccination challenges the body's immune response and can be complicated by hypersensitivity reactions. The autonomic nervous system can modulate the inflammatory immune response, therefore constituting a potential marker to characterize individuals at high risk of hypersensitivity reactions. Autonomic nervous system functionality was assessed through measurement of the heart rate variability (HRV) in subjects with a history of severe allergic reactions and 12 control subjects. HRV parameters included the mean electrocardiograph RR interval and the standard deviation of all normal R-R intervals (SDNN). All measurements were performed immediately before the anti-SARS-CoV-2 vaccination. The median RR variability was lower in the study than in the control group: 687 ms (645-759) vs. 821 ms (759-902); p = 0.02. The SDNN was lower in the study group than in the control group: 32 ms (23-36) vs. 50 ms (43-55); p < 0.01. No correlation was found between age and the SDNN. Autonomic nervous system activity is unbalanced in people with a severe allergy background.

Two-year multidisciplinary follow-up of COVID-19 patients requiring invasive and noninvasive respiratory support.

BACKGROUND: COVID-19 patients frequently develop respiratory failure requiring mechanical ventilation. Data on long-term survival of patients who had severe COVID-19 are insufficient. We assessed and compared two-year survival, CT imaging, quality of life, and functional recovery of COVID-19 ARDS patients requiring respiratory support with invasive (IMV) versus noninvasive ventilation (NIV). METHODS: Patients with COVID-19 pneumonia admitted up to May 28th, 2020, who required IMV or NIV, and survived to hospital discharge were enrolled. Patients were contacted two years after discharge to assess vital status, functional, psychological, and cognitive outcomes using validated scales. Patients with persistent respiratory symptoms or high burden of residual lung damage at previous CT scan received a two-year chest CT scan. RESULTS: Out of 61 IMV survivors, 98% were alive at two-year follow-up, and 52 completed the questionnaire. Out of 82 survivors receiving NIV only, 94% were alive at two years, and 47 completed the questionnaire. We found no major differences between invasively and noninvasively ventilated patients, with overall acceptable functional recovery. Among the 99 patients completing the questionnaire, 23 have more than moderate exertional dyspnea. Chest CT scans showed that 4 patients (all received IMV) had fibrotic-like changes. CONCLUSIONS: Patients who received mechanical ventilation due to COVID-19 and were discharged from hospital had a 96% survival rate at the two-year follow-up. There was no difference in overall recovery and quality of life between patients who did and did not require IMV, although respiratory morbidity remains high.

Efficacy of Cetylpyridinium Chloride mouthwash against SARS-CoV-2: A systematic review of randomized controlled trials.

INTRODUCTION: COVID-19 is a transmissible respiratory and multisystem disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Viral transmission occurs mainly through the spread of salivary droplets or aerosol from an infected subject. Studies suggest that salivary viral load is correlated with disease severity and probability of transmission. Cetylpyridinium chloride mouthwash has been found to be effective in reducing salivary viral load. The aim of this systematic review of randomized controlled trials is to evaluate the efficacy of the mouthwash ingredient cetylpyridinium chloride on salivary viral load in SARS-CoV-2 infection. METHODS: Randomized controlled trials comparing cetylpyridinium chloride mouthwash with placebo and other mouthwash ingredients in SARS-CoV-2 positive individuals were identified and evaluated. RESULTS: Six studies with a total of 301 patients that met the inclusion criteria were included. The studies reported the efficacy of cetylpyridinium chloride mouthwashes in reduction on SARS-CoV-2 salivary viral load compared to placebo and other mouthwash ingredients. CONCLUSION: Mouthwashes containing cetylpyridinium chloride are effective against salivary viral load of SARS-CoV-2 in vivo. There is also the possibility that the use of mouthwash containing cetylpyridinium chloride in SARS-CoV-2 positive subjects could reduce transmissibility and severity of COVID-19.

How many of the COVID-19 deaths occurred in the Intensive Care Unit?

BACKGROUND: The percentage of overall COVID-19 deaths which occurred in intensive care units (ICU) is unknown. We estimated 18% in Italy from February 21, 2020, to February 21, 2021, using cumulative numbers from publicly available databases. This study aims to confirm this percentage using raw data from Italian and European registries. METHODS: We searched PubMed, government health reports, and medical websites to obtain the ratio between number of COVID-19 deaths in ICUs and total number of COVID-19 deaths in the most hit European regions during the first year of the pandemic. When available, we distinguished between different waves and interwaves periods. We performed a forest plot with random effect of proportions to calculate the overall European percentage. RESULTS: We found data for six European countries (United Kingdom, Netherlands, Norway, Italy, Denmark, and Germany). The percentage of COVID-19 deaths which occurred in United Kingdom ICUs was 10% and 11% during the first and the second pandemic waves, respectively. Netherlands and Norway counted 13% and 16%. Italy had 18% of the overall COVID-19 deaths occurring in the ICU during both pandemic waves, and 17% during the intra-pandemic period. Denmark and Germany counted 20% and 22%. Overall, 16% of the COVID-19 deaths occurred in European ICUs. CONCLUSIONS: The percentage of COVID-19 deaths which occurred in European ICUs was 16% and consistent across different countries, ranging from 10% to 22%. Interestingly, we observed no difference between pandemic waves and intra-pandemic periods.

COVID-19 seasonality in temperate countries.

INTRODUCTION: While the beneficial effect of vaccination, restrictive measures, and social distancing in reducing mortality due to SARS-CoV-2 is intuitive and taken for granted, seasonality (predictable fluctuation or pattern that recurs or repeats over a one-year period) is still poorly understood and insufficiently taken into consideration. We aimed to examine SARS-CoV-2 seasonality in countries with temperate climate. METHODS: We identified countries with temperate climate and extracted average country temperature data from the National Center for Environmental information and from the Climate Change Knowledge Portal. We obtained mortality and vaccination rates from an open access database. We used the stringency index derived from the Oxford COVID-19 Government Response Tracker to quantify restriction policies. We used Spearman's and rank-correlation non-parametric test coefficients to investigate the association between COVID-19 mortality and temperature values. We employed multivariate regression models to analyze how containment measures, vaccinations, and monthly temperatures affected COVID-19 mortality rates. RESULTS: The time series for daily deaths per million inhabitants and average monthly temperatures of European countries and US states with a temperate climate had a negative correlation (p < 0.0001 for all countries, 0.40 < R < 0.86). When running multivariate regression models with country fixed effects, we noted that mortality rates were significantly lower when temperature were higher. Interestingly, when adding an interaction term between monthly temperatures and vaccination rates, we found that as monthly temperatures dropped, the effect of the vaccination campaign on mortality was larger than at higher temperatures. DISCUSSION: Deaths attributed to SARS-CoV-2 decreased during the summer period in temperate countries. We found that the effect of vaccination rates on mortality was stronger when temperatures were lower. Stakeholders should consider seasonality in managing SARS-CoV-2 and future pandemics to minimize mortality, limit the pressure on hospitals and intensive care units while maintaining economic and social activities.

One-Year Multidisciplinary Follow-Up of Patients With COVID-19 Requiring Invasive Mechanical Ventilation.

OBJECTIVES: Patients with COVID-19 frequently develop acute respiratory distress syndrome (ARDS) requiring intensive care unit (ICU) admission. Data on long-term survival of these patients are lacking. The authors investigated 1-year survival, quality of life, and functional recovery of patients with COVID-19 ARDS requiring invasive mechanical ventilation. DESIGN: Prospective observational study. SETTING: Tertiary-care university hospital. PARTICIPANTS: All patients with COVID-19 ARDS receiving invasive mechanical ventilation and discharged alive from hospital. INTERVENTIONS: Patients were contacted by phone after 1 year. Functional, cognitive, and psychological outcomes were explored through a questionnaire and assessed using validated scales. Patients were offered the possibility to undergo a follow-up chest computed tomography (CT) scan. MEASUREMENTS AND MAIN RESULTS: The study included all adult (age ≥18 years) patients with COVID-19-related ARDS admitted to an ICU of the authors' institution between February 25, 2020, and April 27, 2020, who received at least 1 day of invasive mechanical ventilation (IMV). Of 116 patients who received IMV, 61 (52.6%) survived to hospital discharge. These survivors were assessed 1 year after discharge and 56 completed a battery of tests of cognition, activities of daily living, and interaction with family members. They had overall good functional recovery, with >80% reporting good recovery and no difficulties in usual activities. A total of 52 (93%) of patients had no dyspnea at rest. Severe anxiety/depression was reported by 5 (8.9%) patients. Comparing 2-month and 1-year data, the authors observed the most significant improvements in the areas of working status and exertional dyspnea. One-year chest CT scans were available for 36 patients; fibrotic-like changes were present in 4 patients. CONCLUSIONS: All patients who survived the acute phase of COVID-19 and were discharged from the hospital were alive at the 1-year follow up, and the vast majority of them had good overall recovery and quality of life.

Outcomes of out-of-hospital cardiac arrest in patients with SARS-CoV-2 infection: a systematic review and meta-analysis.

INTRODUCTION: Out-of-hospital cardiac arrests increased during the COVID-19 pandemic and a direct mechanism of cardiac arrest in infected patients was hypothesized. Therefore, we conducted a systematic review and meta-analysis to assess outcomes of SARS-CoV-2 patients with out-of-hospital cardiac arrest. METHODS: PubMed and EMBASE were searched up to April 05, 2021. We included studies comparing out-of-hospital cardiac arrests patients with suspected or confirmed SARS-CoV-2 infection versus noninfected patients. The primary outcome was survival at hospital discharge or at 30 days. Secondary outcomes included return of spontaneous circulation, cardiac arrest witnessed and occurring at home, bystander-initiated cardiopulmonary resuscitation, proportion of nonshockable rhythm and resuscitation attempted, and ambulance arrival time. RESULTS: In the ten included studies, 18% (1341/7545) of out-of-hospital cardiac arrests occurred in patients with SARS-CoV-2 infection. Patients with out-of-hospital cardiac arrest and SARS-CoV-2 infection had reduced rates of survival (16/856 [1.9%] vs. 153/2344 [6.5%]; odds ratio (OR) = 0.33; 95% confidence interval (CI), 0.17-0.65; P = 0.001; I2 = 28%) and return of spontaneous circulation (188/861 [22%] vs. 640/2403 [27%]; OR = 0.75; 95% CI, 0.65-0.86; P < 0.001; I2 = 0%) when compared to noninfected patients. Ambulance arrived later (15 ± 10 vs. 13 ± 7.5 min; mean difference = 1.64; 95% CI, 0.41-2.88; P = 0.009; I2 = 61%) and nonshockable rhythms (744/803 [93%] vs. 1828/2217 [82%]; OR = 2.79; 95% CI, 2.08-3.73; P < 0.001; I2 = 0%) occurred more frequently. SARS-CoV-2 positive patients suffered a cardiac arrest at home more frequently (1186/1263 [94%] vs. 3598/4055 [89%]; OR = 1.86; 95% CI, 1.45-2.40; P<0.001; I2 = 0%) but witnessed rate (486/890 [55%] vs. 1385/2475 [56%]; OR = 0.97; 95% CI, 0.82-1.14; P = 0.63; I2 = 0%) and bystander-initiated cardiopulmonary resuscitation rate (439/828 [53%] vs. 1164/2304 [51%]; OR = 0.95; 95% CI, 0.73-1.24; P = 0.70; I2 = 53%) were similar. CONCLUSIONS: One-fifth of out-of-hospital cardiac arrest patients had SARS-CoV-2 infection. These patients had low rates of return of spontaneous circulation and survival and were characterized by higher nonshockable rhythms but similar bystander-initiated cardiopulmonary resuscitation rate. REVIEW REGISTRATION: PROSPERO - CRD42021243540.

Impact of COVID-19 Pandemic on Out-of-Hospital Cardiac Arrest System-of-Care: A Systematic Review and Meta-Analysis.

Introduction: COVID-19 pandemic overwhelmed healthcare systems and diverted resources allocated for other conditions. This systematic review and meta-analysis aimed to analyse how the pandemic impacted the system-of-care of out-of-hospital cardiac arrest.Methods: We searched PubMed and Embase up to May 31, 2021, for studies comparing out-of-hospital cardiac arrests that occurred during the COVID-19 pandemic versus a non-pandemic period. Survival at hospital discharge or at 30 days was the primary outcome.Results: We included 24 studies for a total of 75,952 patients. Out-of-hospital cardiac arrests during COVID-19 pandemic had lower survival (19 studies; 603/11,666 [5.2%] vs. 1320/17,174 [7.7%]; OR = 0.54; 95% CI, 0.44-0.65; P = 0.001) and return of spontaneous circulation (4370/24353 [18%] vs. 7401/34510 [21%]; OR = 0.64; 95% CI, 0.55-0.75; P < 0.001) compared with non-pandemic periods. Ambulance response times (10.1 vs 9.0 minutes, MD = 1.01; 95% CI, 0.59-1.42; P < 0.001) and non-shockable rhythms (18,242/21,665 [84%] vs. 19,971/24,817 [81%]; OR = 1.27; 95% CI, 1.10-1.46; P < 0.001) increased. Use of supraglottic airways devices increased (2853/7645 [37%] vs. 2043/17521 [12%]; OR = 1.97; 95% CI, 1.42-2.74; P < 0.001).Conclusions: The COVID-19 pandemic affected the system-of-care of out-of-hospital cardiac arrest, and patients had worse short-term outcomes compared to pre-pandemic periods. Advanced airway management strategy shifted from endotracheal intubation to supraglottic airway devices. REVIEW REGISTRATION: PROSPERO CRD42021250339.

Comorbidities, Cardiovascular Therapies, and COVID-19 Mortality: A Nationwide, Italian Observational Study (ItaliCO).

Background: Italy has one of the world's oldest populations, and suffered one the highest death tolls from Coronavirus disease 2019 (COVID-19) worldwide. Older people with cardiovascular diseases (CVDs), and in particular hypertension, are at higher risk of hospitalization and death for COVID-19. Whether hypertension medications may increase the risk for death in older COVID 19 inpatients at the highest risk for the disease is currently unknown. Methods: Data from 5,625 COVID-19 inpatients were manually extracted from medical charts from 61 hospitals across Italy. From the initial 5,625 patients, 3,179 were included in the study as they were either discharged or deceased at the time of the data analysis. Primary outcome was inpatient death or recovery. Mixed effects logistic regression models were adjusted for sex, age, and number of comorbidities, with a random effect for site. Results: A large proportion of participating inpatients were ≥65 years old (58%), male (68%), non-smokers (93%) with comorbidities (66%). Each additional comorbidity increased the risk of death by 35% [adjOR = 1.35 (1.2, 1.5) p < 0.001]. Use of ACE inhibitors, ARBs, beta-blockers or Ca-antagonists was not associated with significantly increased risk of death. There was a marginal negative association between ARB use and death, and a marginal positive association between diuretic use and death. Conclusions: This Italian nationwide observational study of COVID-19 inpatients, the majority of which ≥65 years old, indicates that there is a linear direct relationship between the number of comorbidities and the risk of death. Among CVDs, hypertension and pre-existing cardiomyopathy were significantly associated with risk of death. The use of hypertension medications reported to be safe in younger cohorts, do not contribute significantly to increased COVID-19 related deaths in an older population that suffered one of the highest death tolls worldwide.