Decreased Heart Rate Variability in COVID-19.

Purpose: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which primarily infects the lower airways and binds to angiotensin-converting enzyme 2 (ACE2) on alveolar epithelial cells. ACE2 is widely expressed not only in the lungs but also in the cardiovascular system. Therefore, SARS-CoV-2 can also damage the myocardium. This report aimed to highlight decreased heart rate variability (HRV) and cardiac injury caused by SARS-CoV-2. Materials and Methods: We evaluated three COVID-19 patients who died. Patients' data were collected from electronic medical records. We collected patient's information, including baseline information, lab results, body temperature, heart rate (HR), clinical outcome and other related data. We calculated the HRV and the difference between the expected and actual heart rate changes as the body temperature increased. Results: As of March 14, 2020, 3 (2.2%) of 136 patients with COVID-19 in Tianjin died in the early stage of the COVID-19 epidemic. The immediate cause of death for Case 1, Case 2, and Case 3 was cardiogenic shock, cardiac arrest and cardiac arrest, respectively. The HRV were substantially decreased in the whole course of all three cases. The actual increases in heart rate were 5 beats/min, 13 beats/min, and 4 beats/min, respectively, less than expected as their temperature increased. Troponin I and Creatine Kinase MB isoenzyme (CK-MB) were substantially increased only in Case 3, for whom the diagnosis of virus-related cardiac injury could not be made until day 7. In all three cases, decreased in HRV and HR changes occurred earlier than increases in cardiac biomarkers (e.g., troponin I and CK-MB). Conclusions: In conclusion, COVID-19 could affect HRV and counteract tachycardia in response to increases in body temperature. The decreases of HRV and HR changes happened earlier than the increases of myocardial markers (troponin I and CK-MB). It suggested the decreases of HRV and HR changes might help predict cardiac injury earlier than myocardial markers in COVID-19, thus its early identification might help improve patient prognosis. Supplementary Information: The online version contains supplementary material available at 10.1007/s44231-022-00024-1.

Decreased Heart Rate Variability in COVID-19

Purpose Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which primarily infects the lower airways and binds to angiotensin-converting enzyme 2 (ACE2) on alveolar epithelial cells. ACE2 is widely expressed not only in the lungs but also in the cardiovascular system. Therefore, SARS-CoV-2 can also damage the myocardium. This report aimed to highlight decreased heart rate variability (HRV) and cardiac injury caused by SARS-CoV-2. Materials and Methods We evaluated three COVID-19 patients who died. Patients’ data were collected from electronic medical records. We collected patient’s information, including baseline information, lab results, body temperature, heart rate (HR), clinical outcome and other related data. We calculated the HRV and the difference between the expected and actual heart rate changes as the body temperature increased. Results As of March 14, 2020, 3 (2.2%) of 136 patients with COVID-19 in Tianjin died in the early stage of the COVID-19 epidemic. The immediate cause of death for Case 1, Case 2, and Case 3 was cardiogenic shock, cardiac arrest and cardiac arrest, respectively. The HRV were substantially decreased in the whole course of all three cases. The actual increases in heart rate were 5 beats/min, 13 beats/min, and 4 beats/min, respectively, less than expected as their temperature increased. Troponin I and Creatine Kinase MB isoenzyme (CK-MB) were substantially increased only in Case 3, for whom the diagnosis of virus-related cardiac injury could not be made until day 7. In all three cases, decreased in HRV and HR changes occurred earlier than increases in cardiac biomarkers (e.g., troponin I and CK-MB). Conclusions In conclusion, COVID-19 could affect HRV and counteract tachycardia in response to increases in body temperature. The decreases of HRV and HR changes happened earlier than the increases of myocardial markers (troponin I and CK-MB). It suggested the decreases of HRV and HR changes might help predict cardiac injury earlier than myocardial markers in COVID-19, thus its early identification might help improve patient prognosis. Supplementary Information The online version contains supplementary material available at 10.1007/s44231-022-00024-1.

Chemotherapy induces ACE2 expression in breast cancer via the ROS-AKT-HIF-1α signaling pathway: a potential prognostic marker for breast cancer patients receiving chemotherapy.

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is a key enzyme of the renin-angiotensin system and a well-known functional receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells. The COVID-19 pandemic has brought ACE2 into the spotlight, and ACE2 expression in tumors and its relationship with SARS-COV-2 infection and prognosis of cancer patients have received extensive attention. However, the association between ACE2 expression and tumor therapy and prognosis, especially in breast cancer, remains ambiguous and requires further investigation. We have previously reported that ACE2 is elevated in drug-resistant breast cancer cells, but the exact function of ACE2 in drug resistance and progression of this malignant disease has not been explored. METHODS: The expression of ACE2 and HIF-1α in parental and drug-resistant breast cancer cells under normoxic and hypoxic conditions was analyzed by Western blot and qRT-PCR methods. The protein levels of ACE2 in plasma samples from breast cancer patients were examined by ELISA. The relationship between ACE2 expression and breast cancer treatment and prognosis was analyzed using clinical specimens and public databases. The reactive oxygen species (ROS) levels in breast cancer cells were measured by using a fluorescent probe. Small interfering RNAs (siRNAs) or lentivirus-mediated shRNA was used to silence ACE2 and HIF-1α expression in cellular models. The effect of ACE2 knockdown on drug resistance in breast cancer was determined by Cell Counting Kit 8 (CCK-8)-based assay, colony formation assay, apoptosis and EdU assay. RESULTS: ACE2 expression is relatively low in breast cancer cells, but increases rapidly and specifically after exposure to anticancer drugs, and remains high after resistance is acquired. Mechanistically, chemotherapeutic agents increase ACE2 expression in breast cancer cells by inducing intracellular ROS production, and increased ROS levels enhance AKT phosphorylation and subsequently increase HIF-1α expression, which in turn upregulates ACE2 expression. Although ACE2 levels in plasma and cancer tissues are lower in breast cancer patients compared with healthy controls, elevated ACE2 in patients after chemotherapy is a predictor of poor treatment response and an unfavorable prognostic factor for survival in breast cancer patients. CONCLUSION: ACE2 is a gene in breast cancer cells that responds rapidly to chemotherapeutic agents through the ROS-AKT-HIF-1α axis. Elevated ACE2 modulates the sensitivity of breast cancer cells to anticancer drugs by optimizing the balance of intracellular ROS. Moreover, increased ACE2 is not only a predictor of poor response to chemotherapy, but is also associated with a worse prognosis in breast cancer patients. Thus, our findings provide novel insights into the spatiotemporal differences in the function of ACE2 in the initiation and progression of breast cancer.

[Clinical study of awake prone positioning treatment in patients with common coronavirus disease 2019 caused by Omicron variant].

OBJECTIVE: To evaluate the clinical effect of awake prone positioning (APP) for common coronavirus disease 2019 (COVID-19) caused by Omicron variant. METHODS: Retrospectively analyze the clinical data of patients with COVID-19 caused by Omicron variant admitted by medical team of Tianjin Third Central Hospital during the period of supporting Tianjin COVID-19 designated hospital from January 8 to February 20, 2022. Patients who met the diagnostic criteria for common COVID-19 and had risk factors for developing severe disease or had pulse oxygen saturation (SpO2) ≤ 0.93 after exercise without supplementary oxygen were enrolled. Patients were divided into APP group and control group according to whether they completed the daily 12-hours APP in the first three days after enrollment. Demographic characteristics, clinical symptoms, COVID-19 vaccination status, laboratory examination, disease progression (progression to severe), time to nucleic acid negative conversion, length of hospital stay, and adverse reactions and tolerability [visual analog scale (VAS) score (the higher the score, the worse the tolerability] during APP were evaluated in two groups. Interleukin-6 (IL-6), C-reactive protein (CRP), SpO2/inhaled oxygen concentration (FiO2) ratio and ROX index (ROXI) were compared between two groups at enrollment, 3rd and 7th day after enrollment. RESULTS: There were no significant differences in demographic characteristics, clinical symptoms, vaccination rates of COVID-19 and laboratory tests between the two groups. There were no statistically significant differences in IL-6, CRP, SpO2/FiO2 ratio and ROXI between two groups at the time of enrollment. Compared with the group at the time of enrollment, SpO2/FiO2 ratio and ROXI in APP group increased significantly at the 3rd day after enrollment [SpO2/FiO2 ratio: 461.90 (457.10, 466.70) vs. 446.67 (437.14, 457.10), ROXI: 25.40 (23.33, 25.93) vs. 22.57 (21.86, 24.40), all P < 0.05], and the levels of IL-6 and CRP in control group were significantly increased [IL-6 (ng/L): 18.30 (6.50, 37.75) vs. 7.40 (5.10, 11.15), CRP (mg/L): 11.46 (2.11, 17.96) vs. 4.11 (1.72, 9.05), all P < 0.05]. At the 3rd day of enrollment, the levels of IL-6 and CRP in APP group were significantly lower than those in control group [IL-6 (ng/L): 7.35 (4.35, 12.80) vs. 18.30 (6.50, 37.75), CRP (mg/L): 4.52 (1.98, 9.66) vs. 11.46 (2.11, 17.96), all P < 0.05], while SpO2/FiO2 ratio and ROXI were significantly higher than those in control group [SpO2/FiO2 ratio: 461.90 (457.10, 466.70) vs. 446.67 (441.90, 459.52), ROXI: 25.40 (23.33, 25.93) vs. 23.31 (22.10, 24.66), all P < 0.05]. At the 7th day of enrollment,there were no significant differences in IL-6, CRP, SpO2/FiO2 ratio and ROXI between two groups. There were no severe cases in both groups. The time of nucleic acid negative conversion and length of hospital stay in APP group were significantly shorter than those in control group [10.0 (8.0, 12.0) days vs. 11.0 (9.0, 13.0) days, 12.0 (10.0, 14.0) days vs. 14.0 (12.0,16.0) days, respectively, all P < 0.05]. The main adverse reaction during APP was back pain, and the incidence in APP group was slightly lower than that in control group, but the difference was not statistically significant [17.9% (17/95) vs. 26.5% (27/102), P = 0.149]. VAS score in control group was significantly higher than that in APP group [score: 2.5 (2.0, 4.0) vs. 2.0 (1.0, 3.0), P = 0.004]. CONCLUSIONS: In common COVID-19 patients caused by Omicron variant with high risk factors for progression to severe disease or decreased oxygen reserve capacity, early APP can shorten the time of nucleic acid negative conversion and the length of hospital stay, but its effect on preventing disease progression cannot be determined.

[Analysis of clinical characteristics of 362 vaccinated or unvaccinated patients infected by novel coronavirus Omicron variant].

OBJECTIVE: To analyze the epidemiological and clinical characteristics of patients infected by novel coronavirus Omicron variant, and also to analyze whether vaccination against novel coronavirus has an impact on the severity and prognosis of Omicron patients. METHODS: A prospective, single-center observational study was conducted to collect data of consecutive patients with Omicron variant infection admitted to the designated hospital for coronavirus disease 2019 (COVID-19) charged by Tianjin COVID-19 rescue medical team of Tianjin Third Central Hospital, from January 8 to February 2, 2022. The clinical characteristics of the patients were analyzed, and the influence of whether the patients were inoculated with booster vaccination on the condition and outcome was analyzed. Data were collected including epidemiological, clinical features, laboratory and imaging examination, treatment measures and clinical outcomes, and difference between groups was analyzed. RESULTS: A total of 362 patients were included, including 136 cases (37.57%) in the booster group, 190 cases (52.49%) in the routine vaccination group, and 36 cases (9.94%) in the unvaccinated group. There was a trend of concentrated distribution of patients, of which 171 cases (47.24%) patients showed family clustering, involving 69 families. Seventy-four cases (20.44%) of the 362 patients had one or more underlying diseases, mainly hypertension (64 cases, 17.68%), diabetes mellitus (23 cases, 6.35%), and coronary heart disease (18 cases, 4.97%); 215 patients (59.39%) had one or more discomfort symptoms, mainly cough (158 cases, 43.65%), pharyngeal discomfort (154 cases, 42.54%) and fever (136 cases, 37.57%). The diagnostic typing was mild type in 194 cases (53.59%), moderate type in 165 cases (45.58%) and severe type in 3 cases (0.83%). The patients had elevated immunoglobulin G (IgG) antibody titers to the novel coronavirus on admission [23.17 (3.08, 60.77)]. Patients were medically isolated and the main treatment measures included traditional Chinese medicine identification (Chinese medicine or tonics) in 265 cases (73.20%), prone treatment in 188 cases (51.93%), anticoagulation with low-molecular heparin in 106 cases (29.28%), immunomodulatory therapy with thymofacine in 21 cases (5.80%), antimicrobial drugs in 20 cases (5.52%), transnasal high-flow oxygen therapy in 12 cases (3.31%), glucocorticoids in 5 cases (1.38%), non-invasive mechanical ventilation in 1 case (0.28%), and invasive mechanical ventilation in 1 case (0.28%). A total of 362 patients were discharged with no deaths, of which 12 patients (3.31%) were admitted to the intensive care unit (ICU). The median duration of illness was 13 (10, 15) days, the median length of hospitalization was 13 (11, 15) days, and the median time to nucleic acid conversion was 13 (10, 15) days. Compared with the unvaccinated group, the IgG antibody titers of patients in the booster and routine vaccination groups [41.49 (20.32, 81.38), 19.94 (2.33, 49.25) vs. 0.16 (0.07, 1.94)] and the proportion of mild patients [66.91% (91/136), 48.94% (93/190) vs. 27.28% (10/36)] were higher, which were also higher in the booster vaccination group than in the conventional vaccination group (all P < 0.05). Compared to the conventional and booster vaccination groups, the unvaccinated group had a higher proportion of severe patients [5.56% (2/36) vs. 0.53% (1/190), 0 (1/136)], longer time to nucleic acid conversion [days: 15 (11, 16) vs.12 (10, 15), 13 (11, 15)], and longer disease duration [days: 15 (11, 16) vs. 12 (10, 15), 13 (11, 15)], and a higher percentage of ICU admissions [16.67% (6/36) vs. 2.63% (5/190), 0.74% (1/136)], with statistically significant differences among the three groups (all P < 0.05). CONCLUSIONS: Omicron variant is extremely infectious with aggregated onset, but its clinical symptoms are mild. The vaccine, especially the booster vaccination, remains effective in preventing severe-stage progression and improving prognosis in patients with Omicron variant infection.

An extended multi-criteria group decision-making method with psychological factors and bidirectional influence relation for emergency medical supplier selection.

The COVID-19 pandemic outbreak spread rapidly worldwide, posing a severe threat to human life. Due to its unpredictability and destructiveness, the emergency has aroused great common in society. At the same time, the selection of emergency medical supplier is one of the critical links in emergency decision-making, so undertaking appropriate decision-making using scientific tools becomes the primary challenge when an emergency outbreak occurs. The multi criteria group decision-making (MCGDM) method is an applicable and common method for choosing supplier. Nevertheless, because emergency medical supplier selection should consider regarding many aspects, it is difficult for decision makers (DMs) to develop a comprehensive assessment method for emergency medical supplier. Therefore, few academics have focused on emergency situation research by the MCGDM method, and the existing MCGDM method has some areas for improvement. In view of this situation, in this study, we propose a new MCGDM method, which considers the bidirectional influence relation of the criteria, consensus and the psychological factors of DMs. It providers a good aid in emergency decision-making and it could apply to other types of MCGDM research. Firstly, DMs give their assessment in interval type-2 fuzzy sets (IT2FSs). Secondly, an extended IT2FSs assessment method and a novel ISM-BWM-Cosine Similarity-Max Deviation Method (IBCSMDM) are used for weighing all alternatives. The TODIM (an acronym for interactive and multi-criteria decision-making in Portuguese) can obtain the ranking results under different risk attenuation factors. Eventually, this extended IT2FSs-IBCSMDM-TODIM method is applied in a real case in Wuhan in the context of COVID-19 to illustrate the practicability and usefulness.