The novel corona virus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), and the disease it causes, COVID-19 (Coronavirus Disease-2019) have had multi-faceted effects on a number of lives on a global scale both directly and indirectly. A growing body of evidence suggest that COVID-19 patients experience several oral health problems such as dry mouth, mucosal blistering, mouth rash, lip necrosis, and loss of taste and smell. Periodontal disease (PD), a severe inflammatory gum disease, may worsen the symptoms associated with COVID-19. Routine dental and periodontal treatment may help decrease the symptoms of COVID-19. PD is more prevalent among patients experiencing metabolic diseases such as obesity, diabetes mellitus and cardiovascular risk. Studies have shown that these patients are highly susceptible for SARS-CoV-2 infection. Pro-inflammatory cytokines and oxidative stress known to contribute to the development of PD and other metabolic diseases are highly elevated among COVID-19 patients. Periodontal health may help to determine the severity of COVID-19 infection. Accumulating evidence shows that African-Americans (AAs) and vulnerable populations are disproportionately susceptible to PD, metabolic diseases and COVID-19 compared to other ethnicities in the United States. Dentistry and dental healthcare professionals are particularly susceptible to this virus due to the transferability via the oral cavity and the use of aerosol creating instruments that are ubiquitous in this field. In this review, we attempt to provide a comprehensive and updated source of information about SARS-CoV-2/COVID-19 and the various effects it has had on the dental profession and patients visits to dental clinics. Finally, this review is a valuable resource for the management of oral hygiene and reduction of the severity of infection. Corona viruses are a diversified class of viruses with zoonotic origin, highly transmitted in humans, causing mild to severe respiratory infections. In 2002 and 2012, respectively, two highly pathogenic coronaviruses emerging in humans were (a) severe acute respiratory syndrome coronavirus (SARS-CoV) and (b) Middle East respiratory syndrome coronavirus (MERS-CoV), causing deadly respiratory illness. At the end of 2019, a novel coronavirus designated as SARS-CoV-2 emerged as a pneumonia of the lower respiratory tract in a patient in Wuhan, China on December 29, 2019 . This viSARS-CoV-2 differs from SARS-CoV due to its higher level of transmissibility and pandemic risk. SARS-CoV-2 has a greater significant reproductive number (R), the statistic used to determine how infectious the agent is, at 2.9. SARS-CoV had an R of 1.77) ,6. It is7 ,6. It The pneumonia-like symptoms of COVID-19 include fever, cough, myalgia or fatigue, and complicated dyspnea. However, there are reported symptoms including headache, diarrhea, hemoptysis, runny nose, and phlegm-producing cough . Symptom0) is between 2.6–4.71 with an average incubation time within the range of 2–11 days [SARS-CoV-2 was first discovered and isolated in Wuhan, China. The virus was isolated from a patient who suffered from pneumonia-like symptoms including fever, cough, and myalgia/fatigue. Three other cases were soon found and the outbreak was linked to a local “wet market”. To confirm the infection source of SARS-Cov-2, Centers for Disease Control and Prevention (CDC) researchers collected 585 samples from the Huanan Seafood Market in Wuhan, Hubei Province, China between January 1–12, 2020. Though the original transmission is thought to be animal-to-human in nature, it is now clear that the virus has adapted a human-to-human transmission pattern. With a now recognized effective reproductive number(R) of 2.9, researchers declared SARS-CoV-2 as one of the more transmissible viruses. Other studies suggested that the basic reproduction range , membrane (M), envelope (E), and nucleocapsid (N). The Spike is a glycoprotein that protrudes from the viral surface, contributing to diversity between coronaviruses, and setting tropism. The Spike is composed of subunits Smembrane .1/S2 that triggers priming and activation [1 assists in the stabilization of the S2 subunit. In contrast, cleavage at this site allows for fusion via conformation changes that were found to be irreversible [1/S2, is believed to make coronaviruses pathogenic [It was proposed that upon binding of the Spike protein, protease cleavage occurs at the Stivation . Upon clversible . The recversible . Yuki etthogenic . Anotherthogenic ,39.According to Yuki et al., Angiotensin Converting Enzyme 2 (ACE-2) was identified as one of the key targets for SARS-CoV 2, in which its expression is high among lung epithelial cells . Shang eThe coronavirus infection triggers endoplasmic reticulum (ER) stress responses in infected cells, associated with increased levels of reactive oxygen species (ROS) and unfolded protein response (UPR). ER stress has an important role in cardiovascular and metabolic disease, obesity and in diabetes. NRF2 (NF-E2-related factor 2) is a redox-sensitive, basic leucine zipper transcriptional factor that upregulates antioxidant gene expression by binding to the promoter region of the antioxidant response element (ARE) . NRF2 coAngiotensin-converting enzyme 2, which is the receptor for SARS-CoV-2, is a regulator of vascular function by modulating nitric oxide (NO) release and oxidative stress ,61. NO rAl-Lami et al. discussed a higher rates of SARS-CoV-2 infection in adult males (~59–68%) compared to females . This obThere is an abundance of information available regarding the effects of pre-existing medical conditions on patients’ COVID-19 infection outcomes. Of the pre-existing conditions that researchers suspect may have an impact on the outcome of patients infected with COVID-19, hypertension has been frequently mentioned. The primary association between patients with pre-existing hypertension and COVID-19 is related to the use of Angiotensin Converting Enzyme (ACE) inhibitors, a common anti-hypertensive medication ,41,60,92In a Japanese study, it was determined that Olmesartan, an Angiotensin Receptor Blocker that is prescribed as an antihypertensive medication, resulted in a higher urinary ACE-2 receptor than individuals not taking the medication ,93. IndiObesity is one of the significant independent risk factor for COVID-19 infection . ObesityCurrent evidence demonstrates that patients with diabetes are more likely to experience severe symptoms and complications than patients without diabetes due to COVID-19 infection. Hyperglycemia facilitates the virus entry into the cells since ACE2 and virus both need glucose for their function . PatientBesides, PD may also be a pre-existing condition that worsens COVID-19 outcomes ,37. InflN = 2195) had contracted COVID-19 infection. This implies that the recommended current PPE and social distancing precautions may be sufficient in dental practices to control transmission of SARS-CoV-2 [As a profession, dentistry deals with the human oral cavity, the main route for the spread of this disease (sneezing and coughing) . This puRS-CoV-2 .In dental practice, prevention of transmission of biological agents take place by use of PPE, decontamination and sterilization procedures. The SARS-CoV-2 virus is sensitive to ultraviolet rays and heat. If exposed to temperatures of at least 56 °Celsius (132.8 °Fahrenheit) for at least 30 min it becomes inactive. Performing a telephone triage with patients to determine if they have symptoms or have come into contact with COVID-19 will allow dental providers the ability to screen patients . If a paWithin the dental community, the psychological impacts of COVID-19 are vast. They affect not only dentists and patients, but also dentists’ family, and staff. As stated earlier, the nature of the profession places dentists at an increased risk of becoming exposed to COVID-19 and spreading it to their patients, families, and peers. Fears that dentists have been reported to experience include carrying the virus to family, getting infected while treating coughing patients, and getting infected by coworkers. These fears can lead patients to undergo treatment delays, which is why it is important to develop psychological coping mechanisms and strategies to keep the practice running .Countrywide shutdowns due to COVID-19 caused many to undergo a mandated quarantine. The effects of quarantine can have severe impacts on an individual. It increases the possibility of psychological and mental problems because people lack interpersonal communication, are distant from those they care about, and psychological treatment resources are severely limited ,112. WitPsychological distress, which often presents as fear amongst dentists, was a common experience during this pandemic. A study reported that many dentists may experience fear, anxiety, concern, sadness, and anger, but only a small percentage (8.7%) feel these intensely . AnotherThe psychological fear that both patients and dentists experience can ultimately influence the patients’ health outcomes. Improvements ibn oral health reduces their risk of developing the non-oral systemic disease . This isAvailable data demonstrate that higher infection rates and the majority of deaths due to COVID-19 occur in assisted living homes and underserved communities due to lack of awareness, education and various psychosocial burdens ,120,121.Korea is an example of implementing psychological well-being in the treatment of COVID-19. Korea has deployed mental health professionals to assist during quarantine because feelings of distress and anxiety can be exacerbated when experiencing symptoms or receiving treatment for COVID-19 . Some stIt is clinically important for oral health professionals to be aware of possible drug interactions that may occur between drugs commonly prescribed in dentistry, in order to prevent adverse reactions that may even endanger the life of a patient with COVID-19.The ongoing pandemic caused by the SARS-CoV-2 virus has proven to be challenging in the pharmaceutical pursuit of a successful drug for treatment. New discoveries unveiling the details of the virus’s biochemical and molecular nature have helped to determine potential drugs for treatment of the COVID-19 infection. However, the need for successful clinical trials to substantiate these drugs remains. Therefore, no official FDA approved drug for the treatment of COVID-19 currently exists. There are currently several drugs being researched for treatment which will be discussed.Perhaps the most promising drug investigated for the treatment of COVID-19 is the antiviral drug known as remdesivir . RemdesiLopinavir is a protease inhibitor that targets the major coronavirus protease, 3CLpro. 3CLpro is responsible for processing the polypeptide translation product from the genomic RNA into the protein components. By blocking 3CLpro the virus is unable to complete normal protein translation and cannot replicate . With ri50 of 0.72 μM,n possibly rendering it more effective at inhibiting the virus in vitro [Chloroquine and hydroxychloroquine are classified as aminoquinolines and are typically used to treat malaria and autoimmune diseases such as systemic lupus erythematosus. In the treatment of SARS-CoV-2 infections, they can block the glycosylation of cell receptors of the virus. They also increases the endosomal pH required for viral fusion and have the potential to be used as broad-spectrum antiviral drugs. The use of these two drugs is included in COVID-19 treatment guidelines internationally; however, additional evidential support is needed. Clinical trials are currently being conducted to assess how safe and effective the drug is against COVID-19. One study with more than 100 patients found that chloroquine was more successful at inhibiting the exacerbation of pneumonia than the control treatment . An addiin vitro . In addition, some of the medicines such as ketoconazole and erythromycin, used for dental treatment may interfere with remdesivir, lopinavir and hydroxychloroquine ,132,133.DMF, the only drug approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) that targets the NRF2/KEAP1 axis , and twoInhaled Nitric Oxide (iNO) is also being developed as a potential treatment for the pulmonary symptoms of COVID-19 . NO is aCorticosteroids such as hydrocortisone and dexamethasone are also being tried out as they have shown some benefits in pneumonia and ARDS patients . CorticoSex steroid hormones, especially estrogen, mount a stronger immune response in females when compared to males. As estrogen levels fall during menopause, women become more vulnerable to numerous health issues, including loss of bone mineral density which can lead to osteoporosis. Around the same time, changes in oral health are also common as teeth and gums become more susceptible to disease, which can lead to inflammation, pain, bleeding, and eventually lost or missing teeth. Estrogen therapy was shown to be effective in reducing tooth and gum diseases in postmenopausal women ,139,140.The drugs described include several possible contenders for treatment of the disease, but more evidence is necessary before an official treatment drug is endorsed. For this to occur, further in vitro, in vivo and clinical trials are warranted to determine the possible roles of the drugs in the management of COVID-19. Research for vaccines and drugs to fight COVID-19 infections has been a priority in most of the world’s institutions. Until an effective vaccine/drug is developed or discovered, reliable and efficient testing has become one of the United States most significant needs. ACE-2 expression has been found to be higher in salivary glands when compared to the lungs. Therefore, SARS-CoV-2 can be detected in saliva earlier and even before lung lesions emerge, and patients can present as asymptomatic carriers. A possible correlation between SARS-CoV-2 infections is the association with sialadenitis. The virus can cause lysis of the acinar cells in the salivary glands leaking salivary amylase into the bloodstream, leading to chronic sialadenitis. Dentists diagnosing sialadenitis may recommend that patients are tested for COVID-19 even though they might not present with the normal symptoms . SalivarSyncope or near-syncope may be a sign of COVID-19 infection ,142. ThiVitamin D  deficiencies have recently been linked to worse prognoses in COVID-19 infections. Vitamin D was found to increase the production of anti-inflammatory cytokines such as defensins and cathelicidins, which in turn mediate the response of the immune system to the infection. Pro-inflammatory cytokines damage lung epithelium and induce the pneumonia-like symptoms associated with a COVID-19 infection. Vitamin D deficiency may be correlated with an increased risk of “cytokine-storm” immune activity. Nutritionists recommend that people at risk of viral infections such as influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3. After a few weeks on this regimen, Vitamin D concentrations should be increased to about 40–60 ng/mL (100–150 nmol/L). For those confirmed COVID-19 positive, a higher dose may be recommended. Research is still ongoing on the effects of Vitamin D and randomized controlled trials and large population studies should be conducted to evaluate these recommendations . VitaminBiomarkers are critical to determining whether interventions are favorable to relieve patients from disease progression. Specific biomarkers such as cardiac and pro-inflammatory cytokines are elevated in some COVID-19 patients and in AA subjects with diabetes, hypertension and cardiovascular disease (CVD) and more recently periodontal disease . Some ofThese and many other new strategies are being developed to combat the spread and effects of COVID-19. With continued perseverance COVID-19 will become a disease that the scientific community has well under control.In conclusion, the SARS-CoV-2 virus has had an indelible effect globally and dentistry is not excluded. New standard protocols are implemented in dental offices worldwide and until an effective vaccine or drug is produced, much of these protocols will remain in effect long-term. A good understanding of the etiology, mechanism of infection, and epidemiology of COVID-19 will help dentists treat their patients. Knowing what co-morbidities increase the risks of fatal COVID-19 outcomes will help dentists better assess what dental procedures are worth the risks of performing on COVID-19 positive patients. In addition, staying abreast of what novel drugs are created to combat the infection is important for dentists. Patients look to dentists not only for oral health advice, though that is their main task; dentists are also expected to provide patients with holistic health advice. Information is generated everyday describing new signs and symptoms of COVID-19. Oral pathologies associated with COVID-19 are still being discovered and could be used in early diagnoses and/or onset of the disease. Research is still being done to look into saliva as a diagnostic tool for the virus. The antibodies associated with saliva and even the expression of certain proteins may be a correlated presence of the virus and can be used as an inexpensive and less invasive way to test and diagnose patients quickly and accurately.


We analysed data from a large provider of long-term care for older people to investigate infection and mortality during the first wave of the pandemic.cohort study of 179 UK care homes with 9,339 residents and 11,604 staff. We used manager-reported daily tallies to estimate the incidence of suspected and confirmed infection and mortality in staff and residents. Individual-level electronic health records from 8,713 residents were used to model risk factors for confirmed infection, mortality and estimate attributable mortality.2,075/9,339 residents developed COVID-19 symptoms , while 951 residents  and 585 staff  had laboratory-confirmed infections. The incidence of confirmed infection was 152.6  and 62.3  per 100,000 person-days in residents and staff, respectively. Sixty-eight percent (121/179) of care homes had at least one COVID-19 infection or COVID-19-related death. Lower staffing ratios and higher occupancy rates were independent risk factors for infection.Out of 607 residents with confirmed infection, 217 died . Mortality in residents with no direct evidence of infection was twofold higher in care homes with outbreaks versus those without .findings suggest many deaths occurred in people who were infected with COVID-19, but not tested. Higher occupancy and lower staffing levels were independently associated with risks of infection. Protecting staff and residents from infection requires regular testing for COVID-19 and fundamental changes to staffing and care home occupancy. In 179 UK long-term care facilities, 10% of residents had laboratory-confirmed infections during the pandemic’s first wave.Confirmed infections had a 36% case fatality rate.Mortality in symptomatic cases was four times the mortality in asymptomatic cases.High occupancy and low staffing were independent risk factors of infection.Globally, the number of coronavirus disease 2019 (COVID-19) cases continues to increase, with substantially higher rates of infection being reported in care homes . Care hoStrategies to protect residents and staff from SARS-CoV-2 include rapid testing, restriction of visitors and vaccination. These require knowledge of the burden of and risk factors for infection in residents and staff in care homes, linked to outcomes, which may only be drawn from evidence from the pandemic’s first wave. Population-based prevalence surveys and studies based on routine data have demonstrated variation in the incidence of infection and case fatality between countries , but manTo our knowledge, there are no studies which have employed population-level active surveillance (daily monitoring to identify possible cases of COVID-19 in residents and staff) in care homes to investigate the epidemiology and clinical outcomes of both suspected and confirmed COVID-19 infections. We analysed electronic health records from the Four Seasons Health Care Group (FSHCG), one of the UK’s largest for-profit providers of residential and nursing care, with the aim of identifying strategies to protect staff and residents in care homes from future waves of infection. Our objectives were to estimate the incidence of and risk factors for infection and incidence of mortality in the following groups: (A) residents with no evidence of infection, (B) symptomatic residents, (C) asymptomatic residents with confirmed infection and (D) symptomatic residents with confirmed infection. We also estimated mortality attributable to COVID-19.Staff and residents living/working in care homes for older people run by the FSHCG between 2 March and 14 June 2020 were eligible for study inclusion. FSHCG provides a combination of residential and nursing care , which is predominantly state-funded. Most residents are permanent, but a small proportion receives temporary (respite) care.Age and Ageing online). 90% of FSHCG homes participated in the whole care home testing programme, implying that all staff and residents were tested for COVID-19 at least once between 11 May and 22 June 2020.In 2020, there were 9,568 beds, representing 9% of all registered care home beds in England, Scotland and Northern Ireland , and were used to categorise residents’ infection status into four groups: (A) residents with no evidence of infection (not tested and/or no symptoms), (B) symptomatic residents (symptoms and not tested or tested negative), (C) asymptomatic residents with confirmed infection (no symptoms but tested positive) and (D) symptomatic residents with confirmed infection (symptoms and tested positive) . The term ‘confirmed’ denoted a positive PCR test. Datix was also used to differentiate deaths in hospital from those in the care home and to identify COVID-19 related deaths. In total, 1,492/1,880 (79%) of Datix reports were successfully linked.FSHCG collects electronic records on residents occupying ‘private’ beds, excluding those occupying beds that are ‘block contracted’ to the local authority  and staff (new symptomatic cases and new confirmed cases). The number of occupied beds in each care home was reported weekly via the same mechanism. COVID-19 related deaths were defined as death in a resident with confirmed infection or a death attributed to COVID-19 by the coroner.Risk factors included individual-level variables  and care home characteristics  obtaineAge and Ageing online.A dummy variable marked the time from which an outbreak occurred, which has been defined throughout the manuscript as a care home recording ≥1 confirmed infection or COVID-19 related death. This definition was preferred over a standard outbreak definition (≥2 cases linked in time/place) to compensate for poor COVID-19 case-ascertainment during the pandemic due to limited testing. Sensitivity analysis using a more specific outbreak definition can be found in Supplementary Methods, Supplementary data are available in Age and Ageing online). The life table allowed us to compute the Kaplan–Meier product limit estimators of the cumulative incidence of symptoms, confirmed infections and COVID-19 related deaths by day based on the aggregate dataset. The incidence rate ratio for care home (based on aggregate data) versus community infections was estimated by contrasting the cumulative incidence for confirmed cases in England with estimates from a national household survey for the period from 11 May to 7 June 2020 . Da. Da13]. une 2020 ,15.Infection incidence was also estimated from the individual-level dataset, but it was subject to under-reporting. Due to this, individual-level data were only used to estimate the age-/sex-specific rates of infection and the Cox proportional hazards models testing the association with individual- and organisational-level risk factors.The aggregate dataset was used to estimate the crude rate of COVID-19 related mortality in residents. Individual-level data were used to estimate the rates of all-cause mortality and case fatality by age and gender.To investigate COVID-19 excess mortality, we made the assumption that residents in ‘non-outbreak’ care homes (no record of any confirmed cases or COVID-19-related deaths) had not been exposed to infection and would therefore not experience excess COVID-19 mortality . A Cox pData were analysed in R3.5.0, epitool  and survThe study included 9,339 residents across England, Scotland and Northern Ireland and 11,604 staff. Out of 179 care homes, 121 homes (67.6%), totalling 7,102 residents, recorded an outbreak. The mean duration of follow-up for residents and staff was 71 days and 82 days, respectively, in the aggregate dataset, and 86 days in the individual-level dataset.Age and Ageing online, Care home managers recorded symptoms of infection in 2,075 residents, contributing to an overall cumulative incidence of 22.2%  or an incidence rate of 368.0 per 100,000 resident-days  (Supplementary Age and Ageing online).Care home managers recorded 526 COVID-19 related resident deaths, which is equivalent to a crude incidence of 5.6%  or 79.7  per 100,000 resident-days. About 24.7% of these deaths took place in the hospital  experiencing symptoms of infection during the study period, while 585  had a confirmed infection  private residents , who accAge and Ageing online). The case fatality rate increased with age and was higher in men.About 217 deaths occurred in residents with confirmed infection, which is equivalent to an all-cause case fatality rate in infected residents (Groups C and D) of 35.7%  . After controlling for other risk factors, increased mortality was independently associated with older age, male gender  and nursing care .Time-dependent Cox proportional hazard models  examinedWe estimated excess mortality in outbreak and non-outbreak care homes, taking individuals with no evidence of infection (Group A) in non-outbreak care homes as the reference group. Hazards of all-cause mortality were twofold higher in Group A—no direct evidence of infection in outbreak versus non-outbreak care homes . All-cause mortality was strongly associated with confirmed infection, whether asymptomatic  or symptomatic . In confirmed infections, mortality was significantly higher in individuals with a record of symptoms.Age and Ageing online). In care homes with outbreaks only, just 161/1014 (16%) deaths attributable to COVID-19 occurred in people with confirmed infection (Groups C and D).Model-based estimates indicate that 653/1,694 (39%) all-cause deaths were attributable to COVID-19  due to under-ascertainment caused by the lack of testing. However, it is possible that we incorrectly classified some care homes, with only a few cases throughout the pandemic as having experienced outbreaks. Other key limitations relate to the completeness of individual-level data. We lacked information on co-morbidity and ethnicity, which have been shown to be important risk factors for adverse outcomes in COVID-19 , but we UK numbers of infected residents and staff were underestimated during the first wave of the pandemic. Our findings support disease control strategies which integrate public health surveillance and rapid testing with investment in care homes to reduce occupancy and increase staffing. Although testing will improve case ascertainment, frequent testing in care home residents may not always be desirable if the risk of infection is low because the testing procedure  is invasive and may distress vulnerable residents. Since the incubation period and serial interval of COVID-19 is short , the intaa-21-0014-File002_afab060Click here for additional data file.aa-21-0014-File003_afab060Click here for additional data file.


Since the outbreak of COVID-19 in China at the end of 2019, the world has experienced a large-scale epidemic caused by the SARS-CoV-2. The epidemiological and clinical course of COVID-19 patients has been reported, but there have been few analyses about the characteristics, predictive risk factors, and outcomes of critical patients. In this single-center retrospective case–control study, 90 adult inpatients hospitalized at Tongji Hospital  were included. Demographic, clinical, laboratory tests, and treatment data were obtained and compared between critical and non-critical patients. We found that compared with non-critical patients, the critical patients had higher SOFA score and qSOFA scores. Critical patients had lower lymphocyte and platelet count, elevated D-dimer, decreased fibrinogen, and elevated high-sensitivity C-reactive protein (hsCRP), and interleukin-6(IL-6). More critical patients received treatment including antibiotics, anticoagulation, corticosteroid, and oxygen therapy than non-critical ones. Multivariable regression showed higher qSOFA score and elevation of IL-6 were related to critical patients. Antibiotic usage and anticoagulation were associated with decreased in-hospital mortality. And critical grouping contributed greatly to in-hospital death. Critical COVID-19 patients have a more severe clinical course. qSOFA score and elevation of IL-6 are risk factors for critical condition. Non-critical grouping, positive antibiotic application, and anticoagulation may be beneficial for patient survival. This disease has also spread to 216 countries, areas or territories, with a total of 23,311,719 infected cases and 806,410 confirmed deaths2. The World Health Organization (WHO) has claimed COVID-19 as a global pandemic3. And health systems in all countries are currently faced with serious challenges.Since the outbreak of COVID-19 in Wuhan, Hubei at the end of 2019, China has experienced another large-scale epidemic disease caused by a coronavirus after Severe Acute Respiratory Syndrome (SARS). By the end of August 24, 2020, the number of confirmed cases in China exceeded 8, 4981, with more than 4600 deaths4, patients can be divided into four types clinically: mild, ordinary, severe and critical. The clinical manifestation and required treatment vary greatly between different types. Mild and ordinary patients need only supportive treatment, and self-healing cases have been reported, but most of the critically ill patients need mechanical ventilation or even extra-corporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT). The mortality rate reported in different literatures is between 1–4%7, but the severity of the illness and the mortality rate can be underestimated due to a large number of asymptomatic infections and mild patients. Most current researches are descriptive studies on patients admitted to hospitals, yet there have been few analyses about the outcomes and risk factors of critical patients until now.Although we have acquired a deeper understanding of the disease through autopsy and virological study, no specific treatment seems to be definitive and effective for preventing the disease progression and death of critical patients. According to the diagnosis and treatment guidelines released by China Health and Medical CommissionHere, we present the clinical course and outcomes of a group of critical patients with COVID-19, and attempt to identify risk factors for disease progression and in-hospital mortality in these patients. We aim to find some predictive risk factors for early warning, to provide opportunities for timely medical intervention by simple and effective assessment.We collected 90 inpatients diagnosed with COVID-19 at the Tongji Hospital  from Jan 28th to Feb 28th. Of all the patients, 45 are critical patients and 45 are non-critical patients. All patients were discharged or died before the date of data collection. 32 of the 90 patients died and 48 were discharged.  and respiratory rate , higher SOFA score  and qSOFA score. More patients in the critical group had symptoms of fever, expectoration, and dyspnea, but most of the symptoms like cough, fatigue, chill, etc. were non-specific and showed no significance between groups .The mortality rate in the critical group was 67%, which was significantly higher than the non-critical group. The median time from onset to admission in the critical group was 16 days (10–25), longer than that in the non-critical group. There was no significant difference in the time of hospitalization and the entire course of disease between the two groups.9/L) and neutrophil count  and lower lymphocyte count. Platelet counts are also lower. Elevated alanine aminotransferase , total bilirubin , hypoalbuminemia , and hyperureaemia  were also more commonly observed in the critical group. Meanwhile, critical patients are more likely to show prolonged partial thromboplastin time , increased D-dimer, and decreased fibrinogen. In terms of inflammatory factors, the proportion of patients with elevated ferritin and elevated hsCRP and IL-6 in the critical group was also larger.Results of blood test at admission for all patients were obtained and analyzed Table .. It wasMore than two-thirds of the 90 patients (n = 62) received varying level of oxygen therapy support, of which 36 patients had mechanical ventilation. The critical group has higher requirements for oxygen therapy support. More patients need high-flow oxygen inhalation, prone ventilation, BiPAP and mechanical ventilation. The usage of antiviral drugs is similar between the two groups. More patients were treated with antibiotics, intravenous immunoglobin (IVIG), and glucocorticoid in the critical group; more critical patients received treatment for complications, including renal replacement therapy and anticoagulation. 6 of the patients received anti-IL-6 treatment (5 died) and 4 received ECMO (3 died).To find the possible indicators for patients’ group, potential influential factors including differences between the two groups and factors related to clinical diagnosis and treatment were screened. Age, gender, qSOFA scores, low lymphocyte (less than 0.8), high D-dimers (greater than 1), and high IL-6 (greater than twice the upper limit) were analyzed in conditional logistic regression using COX survival analysis. We found that qSOFA scores and increased IL-6 were significantly associated with critical group Table .Table 3R8, which supported our findings that corticosteroid (p = 0.016), non-invasive ventilation (p = 0.014) and invasive ventilation (p < 0.001) were considered to be linked with in-hospital mortality. Then, five factors, especially treatment factors, were selected in multivariate regression analysis, among which age, disease grouping, antibiotics and anticoagulation were related to death. . Corticosteroid was the first reported drug that can lower 28-day mortality of patients hospitalized with COVID-19 among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support p = 0.01 and inva10. This is consistent with our observations during clinical process.COVID-19 has now become a global pandemic, and medical systems in many countries are facing serious challenges. Survival of critical and non-critical patients are significantly different, so the early identification of critical patients is very important. This retrospective research shows that critical patients have more severe clinical situation and worse prognosis, which requires medical support of high grade, including higher level of oxygen therapy, supportive therapy and organ replacement therapy. As seen in other literatures, the risk of complications is also higher in critical patients, including respiratory failure, acute respiratory distress syndrome (ARDS), secondary infections, myocardial injury, liver and kidney dysfunction, etc.11, indicating a more severe bone marrow suppression and lymphocyte failure12. In addition, worse coagulation function is more likely to occur in critical patients, and the disseminated intravascular coagulation (DIC) indicators like platelet count, PT, and D-dimer have changed significantly. Acrotic gangrene was observed in several patients (not shown in the data), indicating a potential DIC. By comparing the pathogenesis of SARS, MERS, and other viral pneumonias, we find that some critical patients may need low-molecular-weight heparin anticoagulant therapy13. During our clinical practice, the gangrene in critical patients did significantly improve after low-molecular-weight heparin treatment. Also, data analysis also provided supportive evidence that anticoagulation may be beneficial for patient outcomes.There are several clinical manifestations worth mentioning. For example, dyspnea is not the most significant symptom of COVID-19, but it is relatively prominent in critical patients, so it may be a suggestive clue. Critical patients have significantly lower lymphocytes compared with non-critical ones, which is consistent with autopsy results9, we have found that high qSOFA scores and IL-6 elevation may help to identify critical patients. The qSOFA score can make quick evaluation of patient condition based on vital signs and consciousness14. Although previous research revealed that qSOFA score may have limited utility for predicting mortality in an ICU setting compared with SOFA score or SIRS criteria15, we believe that its convenience may have great value for practical application in current situation especially for primary medical institutions and emergency with insufficient medical resources. The elevation in IL-6 suggests the possible role of cytokine storm in the progression of COVID-19 and potential therapeutic targets16.In addition to the risk factors like elder age that have been reported17, but the balance between the suppressive effects of glucocorticoid on immunity and the positive effects of its anti-inflammatory role requires further research.Treatment is another field we paid attention to, although no specific treatment has been proven effective. We mainly provided supportive treatment according to clinical symptoms. The use of more antibiotics in critical patients, combined with relatively high neutrophil count, indicates more possibility of secondary opportunistic or drug-resistant infections during the long period of disease and mechanical ventilation. Pathological examination also confirmed that bacterial infection is an important pathological process which may aggravate alveolar injury and ventilation dysfunction among dead patients. Multivariate regression analysis showed that positive antibiotic usage may be beneficial for patient outcomes. Glucocorticoid is another controversy. Although it can be used as an anti-shock and anti-inflammatory agent, the use of glucocorticoid may contribute to infection. The experience of SARS has deepened our understanding of the role of glucocorticoid in severe viral pneumonia18, as many clinical trials are still ongoing. We are urgently expecting some promising results, which is of vital importance in clinical course.This study will provide possible supportive evidence for potential treatments by comparing effect made by different treatments on patients’ survival curves. Antiviral drugs, anti-IL-6 therapy and proper glucocorticoid usage may all have potential therapeutic effectsOur study has some limitations. First, only 90 patients with confirmed COVID-19 were included; the suspicious and undiagnosed cases were excluded in the analyses. It would be better to absorb more patients to gain a comprehensive understanding of 2019nCoV. Second, the lack of availability to some medical records limited our analyses of certain data. Some blood tests have not been performed in all patients for realistic reasons. In addition, since some of the critical patients were transferred to our hospital in urgent need for medical support due to the outbreak of COVID-19, it is difficult to evaluate the effect of previous treatment, and may lead to some unknown bias to sample selection. Moreover, this study is a retrospective case–control design of a single center and a rather small sample size may limit our selection of potential risk factors in the multiple regression analysis to some degree. The possibility of selection bias may exist and the results need careful interpretation.In conclusion, this study compared the clinical characteristics between critical and non-critical COVID-19 inpatients, and qSOFA score and elevation of IL-6 are risk factors for critical condition. In multivariate survival analysis, the treatment of antibiotics and anticoagulation were significant factors for in-hospital mortality.This study is a retrospective case–control study, including adult (≥ 18 years old) inpatients hospitalized at Tongji Hospital  from Jan 9th to Feb 28th. All adult patients who were diagnosed with COVID-19 according to WHO interim guidance were screened. All patients were discharged or died before the date of data collection. These patients were divided into critical and non-critical group which include mild, ordinary and severe patients. The diagnosis was made according to the diagnosis and treatment guidelines (7th ed) released by China Health and Medical Commission. Mild patients are defined as patients with minor clinical symptoms and no imaging manifestations. Ordinary patients are defined as patients with typical clinical and imaging manifestations. Severe patients are defined as patients meeting at least one of the following criteria: respiratory rate over 30/min, SpO2 less than 93% at rest, PaO2/FiO2 less than 300 mmHg, rapidly progressive lung imaging lesions. Critical patients are defined as patients who need mechanical ventilation or shock or have other organ failure.The criteria for discharge were absence of fever for at least 3 days, substantial improvement in both lungs in chest CT, clinical remission of respiratory symptoms, and two throat-swab samples negative for SARS-CoV-2 RNA obtained at least 24 h apart.Personal identifiable information was removed from all cases during the study to protect privacy. The study was approved by the Research Ethics Commission of Tongji Hospital  and the requirement for informed consent was waived by the Ethics Commission. All methods were performed in accordance with the relevant guidelines and regulations.Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were extracted from electronic medical records in the hospital form by two physicians independently using a standardized collection. The data consistency and accuracy were checked by a third researcher.Methods for laboratory confirmation of COVID-19 have been described elsewhere. According to the latest guideline, COVID-19 can be diagnosed by either serum antibody or nucleic acid detection. The SARS-CoV-2 RNA was detected by Centers for Disease Control and Prevention, and the detection of serum antibody was done by local health institutions.Routine blood examinations were complete blood count, coagulation profile, serum biochemical tests , myocardial enzymes, inflammatory factors (including high-sensitivity C-reactive protein (hsCRP), interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10(IL-10) tumor necrosis factor α (TNF α) and serum ferritin), and procalcitonin. Baseline examination data were obtained for all patients. Frequency of examinations was determined by the treating physician according to disease progression.The continuous data were expressed by mean (SD) or median (IQR) depending on whether they are normally distributed. They were tested by t-test or Mann-Whitey U test depending on normal distribution and homogeneity in variance. The Shapiro–Wilk test was used to test whether the continuous data were normally distributed. Categorical data were expressed by number (percentage), tested by Chi-square or Fisher’s exact test. Multivariant analysis used logistic regression. For survival analysis, univariant analysis was Kaplan–Meier analysis, and multivariant analysis was COX regression. The significance was defined as p value below 0.05. All the data analysis was conducted in SPSS 21.0.


We report the case of a middle-aged woman who developed trigeminal neuralgia as a sequela of multiple sclerosis (MS). The trigeminal neuralgia was refractory to medications and persisted for two years. Eventually, it was resolved by a mandibular nerve block followed by natalizumab administration. The pain was controlled for 23 months, and additional nerve blocks were not required during this period. It has been previously reported that natalizumab therapy improves the Expanded Disability Status Scale (EDSS) scores and health-related quality of life in patients with MS. In the present case, natalizumab may have prolonged the effect of the mandibular nerve block and consequently improved the patient’s quality of life. Multiple sclerosis (MS) is a major inflammatory and demyelinating disease of the central nervous system and is associated with autoimmune mechanisms. Trigeminal neuralgia can often complicate the clinical course of MS . The patHere, we describe the successful treatment of debilitating drug-refractory trigeminal neuralgia by a single mandibular nerve block followed by natalizumab administration in a middle-aged woman with MS.A 48-year-old woman was admitted to our hospital due to drug-refractory trigeminal neuralgia. At 31 years of age, she had experienced double vision and tetraparesis after giving birth to her second child. Since then, she had experienced relapses twice a year and had been diagnosed with relapsing-remitting MS. She had been prescribed interferon b-1b; however, she could not continue the treatment because of the onset of depression. Since interferon b-1b had been the only disease-modifying drug sold at that time, her treatment had been switched to prednisolone (15 mg/day) and azathioprine (50 mg/day). This treatment had been ineffective, and she had continued to experience relapses twice a year. At 43 years of age, she was confined to a wheelchair. At 46 years of age, she had developed drug-refractory trigeminal neuralgia with demyelinating brainstem lesions that caused sustained, strong right-sided pain at the back of the tongue and consequently affected her oral intake and daily life activities. An MRI showing the extent of her brainstem lesions is shown in Figure At 48 years of age, the patient was admitted to our hospital. Neurological examination revealed drug-refractory trigeminal neuralgia with strong right-sided pain at the back of the tongue, lower lip, and chin; right-sided hypoesthesia in the lower lip; diplopia; bilateral medial longitudinal fasciculus (MLF) syndrome; moderate spastic tetraparesis; moderate ataxia; and paresthesia and hypoesthesia in the right upper and both lower extremities. Her blood tests were negative for inflammatory markers and autoantibodies, including anti-aquaporin 4, anti-nuclear, and anti-dsDNA antibodies. The cerebrospinal fluid analysis revealed a normal white blood cell count (0/µL), protein level (29 mg/dL), and myelin basic protein level (<31.2 pg/mL), although the immunoglobulin G index was elevated (0.87) and oligoclonal IgG bands were present.Brain T2-weighted imaging demonstrated multiple high-intensity lesions in the brainstem, including the intramedullary running path of the trigeminal nerve. The lesions exhibited no gadolinium enhancement Figure -1C.The lesions involved the right trigeminal nerve tract, but vascular compression at the entry of the trigeminal nerve root was not recognized on fast imaging employing steady-state acquisition (FIESTA). In addition, brain T2-weighted imaging showed high-intensity lesions in the periventricular and subcortical white matter. T1-weighted imaging showed that many of these lesions were hypointense Figure -2C.Spinal cord T2-weighted imaging showed 11 high-intensity white matter lesions with a length equivalent to less than 1.5 vertebral bodies Figure , 3B.The patient was diagnosed with trigeminal neuralgia due to relapse of MS. The trigeminal neuralgia was refractory to medications such as carbamazepine, levetiracetam, acetaminophen, tramadol, and morphine. Therefore, an anesthesiologist administered a mandibular nerve block with radiofrequency thermocoagulation. The needle was inserted at an extraoral point 4 cm from the corner of the mouth and advanced to the foramen ovale. Coagulation was performed at 80 °C for 180 s after a trial with a local anesthetic. Her pain resolved  . She resNatalizumab treatment was continued without additional nerve blocks, and she did not experience pain or develop new demyelinating lesions for 23 months Figure .We derived two important findings from the present case. First, a single mandibular nerve block could resolve the pain of trigeminal neuralgia associated with MS with no relapses for 23 months. Second, natalizumab treatment may have prolonged the pain-relieving effects of the nerve block, thus resulting in an improved quality of life.Although a single nerve block can result in an improvement in approximately 95% of the patients, it should be noted that the effect of mandibular nerve block is not permanent . MoreoveThe pathophysiology of trigeminal neuralgia remains unclear, although the main theory is that chronic inflammatory processes in the central nervous system cause secondary trigeminal neuralgia, including that associated with MS . In thisAlthough disease-modifying drugs such as natalizumab are widely used and work by interacting with the immune system, they are not routinely used for symptomatic treatment of sequelae that often occur as a result of MS. To date, no study has evaluated the effects of immunotherapy for trigeminal neuralgia. However, natalizumab treatment reportedly decreases the relapse rate and stabilizes disability levels in MS . In addiThe findings from this case suggest that mandibular nerve block followed by natalizumab therapy is effective in controlling MS-associated trigeminal neuralgia, which, to date, has been generally treated with combination treatment involving carbamazepine, nerve blocks, and surgery.


Whether the risk of multidrug-resistant bacteria (MDRB) acquisition in the intensive care unit (ICU) is modified by the COVID-19 crisis is unknown. In this single center case control study, we measured the rate of MDRB acquisition in patients admitted in COVID-19 ICU and compared it with patients admitted in the same ICU for subarachnoid hemorrhage (controls) matched 1:1 on length of ICU stay and mechanical ventilation. All patients were systematically and repeatedly screened for MDRB carriage. We compared the rate of MDRB acquisition in COVID-19 patients and in control using a competing risk analysis. Of note, although we tried to match COVID-19 patients with septic shock patients, we were unable due to the longer stay of COVID-19 patients. Among 72 patients admitted to the COVID-19 ICUs, 33% acquired 31 MDRB during ICU stay. The incidence density of MDRB acquisition was 30/1000 patient days. Antimicrobial therapy and exposure time were associated with higher rate of MDRB acquisition. Among the 72 SAH patients, 21% acquired MDRB, with an incidence density was 18/1000 patient days. The septic patients had more comorbidities and a greater number of previous hospitalizations than the COVID-19 patients. The incidence density of MDRB acquisition was 30/1000 patient days. The association between COVID-19 and MDRB acquisition (compared to control) risk did not reach statistical significance in the multivariable competing risk analysis (sHR 1.71 (CI 95% 0.93–3.21)). Thus, we conclude that, despite strong physical isolation, acquisition rate of MDRB in ICU patients was at least similar during the COVID-19 first wave compared to previous period. The respiratory infection COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide, being considered pandemic by the World Health Organization since 11 March 2020 [During this pandemic, health care systems worldwide became overloaded and experienced shortages of intensive care unit (ICU) beds  and protAMR is a major health problem , responsHowever, until now, the risk of MDRB acquisition in the ICU during COVID-19 crisis remains unknown; whether this risk of MDRB acquisition is higher in COVID-19 units compared to normal functioning ICU has not been studied. The aim of this study is to describe the rate of MDRB acquisition in COVID-19 ICUs compared with the MDRB acquisition in the same department before the COVID-19 crisis. We conducted a single center retrospective case–control study of COVID-19 patients admitted to the ICUs of Erasme Hospital, Brussels, Belgium from March to April 2020. This research was carried out following the rules of the Declaration of Helsinki and was approved by Erasme Hospital Ethics Committee under the protocol number P2020/371. Due to the retrospective nature of the study the need for informed written consent was waived.Staphylococcus Aureus (MRSA), Extended Spectrum Beta-Lactamase (BLSE), Carbapenemase-Producing Enterobacterales (CPE) and Vancomycin Resistant Enterococci (VRE) is indicated at the room door and requires health care workers to wear gloves and gown before entry. We have a meeting with the antibiotic stewardship team twice a week.Under normal circumstances, our ICU operates with 30 beds divided into five ICUs with 6 single rooms each. We perform nasal and rectal surveillance cultures upon ICU admission and twice a week thereafter. Colonization by Methicillin Resistant During COVID-19 crisis, we increased our ICU beds from 30 to 39, by opening 5 beds in the existing ICUs and building another 4-bed ICU in two operating rooms. Only one 6-bed ICU remained available for non-COVID-19 admissions. The remaining 33 beds were reserved for COVID-19 patients with a high risk of invasive mechanical ventilation. Patients with stable clinical condition on CPAP remained in the wards. All patients admitted to the COVID-19 ICUs of Erasme Hospital between 15/03 and 30/04, regardless of the final etiological diagnosis, were eligible for inclusion; the sole exclusion criterion was an ICU stay <48 h. These patients were considered as cases and are named COVID-19 patients in this manuscript.The admission to the non-COVID-19 ICU was scarce during the study period. Therefore, it was not possible to use this population as control. Given the unusual duration of mechanical ventilation in COVID-19 patients  we compaDemographic data and severity scores were collected at ICU admission. We defined the length of exposure as the duration between ICU admission and the day of MDRB acquisition, or between ICU admission and ICU discharge in patients without MDRB acquisition. We collected the following data during the exposure time: antimicrobial use, presence of central venous catheter, urinary tract catheter, mechanical ventilation and the occurrence of surgery. The primary endpoint was the rate acquisition of MDRB in the COVID-19 units. We considered patients MDRB+ when a MDRB was found in any microbiological specimen. Patients that were MDRB+ within 48 h after admission were considered index cases. Patients that acquired MDRB during ICU stay were considered new cases. Patients that did not acquire MDRB during ICU stay were considered MDRB-. We collected the presence of possible cross-transmission. Cross-transmission was suspected if a patient acquired a MDR pathogen with the same antimicrobial susceptibility and resistance mechanism than another patient hospitalized at the same time in the same unit.In our center, we perform routine surveillance cultures  on admission and then twice a week throughout the ICU stay. ® CARBA SMART agar  for the detection of carbapenemase-producing Enterobacteriaceae; MacConkey agar containing ceftazidime  for the detection of third generation cephalosporin-resistant Pseudomonas aeruginosa, Klebsiella spp. and Enterobacter spp.; chromID® VRE agar for the detection of Vancomycin-resistant Enterococcus faecium. Identification of MDRB is performed using matrix-assisted laser desorption/ionization time-of-flight analysis (MALDI–TOF). For MDRB detection, rectal swabs are streaked onto selective plates as follow: chromIDEnterobacteriaceae and ampC de-repression were identified using detection of synergy on disk diffusion test as recommended by EUCAST. For methicillin-resistant S. aureus detection, nasopharyngeal swabs were streaked onto ChromID® MRSA selective plates. MDR Pseudomonas and Acinetobacter spp. were defined as recommended considering antimicrobial resistance phenotype [Antimicrobial resistance was defined according to breaking points recommended by the European Committee on Antimicrobial Susceptibility Testing (EUCAST)  using VIhenotype .Categorical variables are reported as count (%), continuous data that were normally distributed as mean ± standard deviation (SD) and skewed data as median (interquartile range). t-test, Mann–Whitney test, χ2 test or Fisher’s exact test, as appropriate. In order to identify factors associated with the acquisition of MDRB, we compared patients admitted to COVID-19 ICUs with the SAH patients admitted to our ICUs in previous years (2016–2019); however, a comparison was not done with septic shock patients as not all COVID-19 patients could be matched. Cumulative incidence function of the acquisition of MDRB was used to describe the probability of MDRB acquisition at a given time. The Gray’s test was used to test for the differences. Univariate and multivariable regression analyses were performed using the Fine and Gray competing risks proportional hazards regression model. Death was considered as a competing risk factor for the development of MDRB. In the multivariable model only variables that had p-value less than 0.2 by univariate analysis were considered. Incidence of MDRB acquisition was calculated by dividing the number of new cases by the total number of patients admitted to the COVID-19 ICUs. The incidence rate was calculated by dividing the number of new cases by the total number of patient days in the COVID-19 ICUs. The same calculations were done for the two historical control cohorts and after splitting them into tertiles according to admission periods. We compared MDRB+ and MDRB– patients in the COVID-19 cohort using Student’s p-value < 0.05 was considered as statistically significant. Data were analyzed using IBM® SPSS® Statistics software, version 26 for Macintosh .All tests were two-tailed and a We identified 75 patients admitted to COVID-19 units during the studied period. Three patients were excluded (ICU stay <48 h) letting 72 included patients representing 1104 patient days of exposure. COVID-19 was diagnosed in 69 out of the 72 patients ; the remaining three non-documented COVID-19 patients were kept in the analysis. Of note, five patients (7%) were MDRB carriers at ICU admission. Fifty-two patients (72%) were treated with mechanical ventilation. The median ICU LOS in survivors was 33 days (16–52). Enterobacteriaceae. No MRSA were isolated. We identified 16/31 (52%) suspected cross-transmission events involving mainly ESBL K. pneumoniae, AmpC derepressed E. aerogenes and Vancomycin-resistant E. faecium. MDRB positive and negative patients had similar demographic characteristics and severity at admission. Exposure time was longer in MDRB+ patients and antimicrobial therapy was more frequently used. The most frequently used antimicrobial treatment was piperacillin/tazobactam, and its use was associated with a non-significantly higher rate of MDRB acquisition  acquired 31 MDRB (seven patients acquired more than one MDRB) during their ICU stay. The incidence density of MDRB acquisition was 30/1000 patient days. uisition . SteroidIn terms of clinical outcome, ICU and hospital mortality were similar between the two groups. These results are shown in To evaluate if the MDRB acquisition risk had changed during COVID-19 pandemic, we compared the COVID-19 patient cohort with a retrospective cohort of SAH patients hospitalized in the same ICU matched on the need for mechanical ventilation and the ICU LOS. Characteristics of both cohorts are shown in p = 0.2) than in COVID-19 patients. The MDRB distribution is shown in In SAH patients, the proportion of patients with MDRB acquisition was lower  ,  = 0.08) . The uniIn this retrospective cohort of patients admitted to COVID-19 ICUs for suspected or confirmed SARS-CoV-2 infection, the incidence density of MDRB acquisition during ICU-stay was 30/1000 patient days. After adjustment and competitive risk analysis, the risk of MDRB acquisition tended to be higher, although not reaching statistical significance, in COVID-19 ICUs compared to control usual ICU.The interpretation of such results must take into account the rate of acquisition of MDRB in the control group. Indeed, it is highly dependent on local parameters, and thus may vary greatly across centers and countries . In anotOur study was not designed to explore whether the risk of MDRB acquisition is related to the COVID-19 per se or to the disruption in hospital functioning during the pandemic crisis. In the hospital setting, dissemination of MDRB happens through either cross-transmission or environmental sources, being favored at the individual level by antimicrobial therapy selection pressure . In the The possibility of dissemination of MDRB during a viral pandemic had been theoretically mentioned , but as The high rate of MDRB acquisition may be explained by several factors related to the pandemic: shortage of PPE , work ovBeside infection control measures, an increase in the use of antimicrobials is also a well-known factor associated with MDRB acquisition . PatientOur study has several limitations. First, generalization may be difficult since these results may depend on our center’s characteristics. Second, we selected a control group without acute respiratory failure. However, ARDS patients are usually older and have more comorbidities than COVID-19 patients . MoreoveThe rate of MDRB acquisition was high in patients admitted in ICU during COVID-19 first wave. After adjustment, the risk of MDRB acquisition when being admitted to COVID-19 units was higher, but did not reach statistical significance, compared to control patients hospitalized for SAH before the pandemic and matched on ICU LOS and the use of mechanical ventilation. Larger multicentric studies will be necessary to assess how the viral pandemic impacted the MDRB one.


Asherman’s syndrome (AS) is characterized by intrauterine adhesion or fibrosis resulting from damage to the endometrium, often leading to amenorrhea, infertility, or recurrent pregnancy loss. Although various therapeutic strategies for AS have been proposed, the options remain limited. New strategies such as bone marrow-derived mesenchymal stem cell (BM-MSC) therapy aim to potentiate the intrinsic capacity of endometrial regeneration. However, BM-MSC therapy has not been widely adopted mainly because it involves invasive and expensive procedures such as bone marrow biopsy and cell storing. On the other hand, platelet-rich plasma (PRP) is considered safe and affordable because it involves the less invasive procedure of blood collection from peripheral veins to produce PRP. To assess the effectiveness of human PRP infusion for endometrial regeneration, we established a murine model of injury-induced AS and evaluated endometrial morphology, expression of fibrosis-related factors, implantation sites (IS), and pregnancy outcomes associated with human PRP treatment. We found that treatment with human PRP was associated with improved endometrial morphology, reduced degree of fibrosis, and down-regulated expression of fibrosis-related factors in murine model of AS. Furthermore, human PRP treatment was associated with a higher number of IS and live-births. Our results suggest that human PRP treatment may become a valuable strategy to promote the regeneration of damaged endometrium and thus improve fertility and pregnancy outcomes in clinical practice. The human endometrium undergoes cyclic regeneration and breakdown during the reproductive years of a woman’s life . The endL-arginine, colony-stimulating factor, and cytokines; however, such strategies have had limited success (In Asherman’s syndrome (AS), injury to the endometrium due to repeated or aggressive curettage or endometritis causes dysfunction of the endometrial regeneration process, resulting in loss of functional endometrium and obliteration of the uterine cavity due to intrauterine adhesion . Women w success . Recentl success . In part success . While v success . It is dPlatelet-rich plasma (PRP) infusion can promote tissue regeneration in patients with various clinical conditions including ulcers, burns, muscle damage, and bone disease, as well as in patients recovering after surgery . PRP is To evaluate the potential pharmacologic use of human PRP in the clinical setting, we developed a murine model of AS and conducted histological, biological, and functional analysis to investigate whether human PRP administration could restore endometrial function and improve pregnancy outcomes.This study was approved by the Institutional Review Board  of the CHA Gangnam Medical Center. For PRP preparation, blood samples were obtained after the donors provided informed consent. All donors are Asian females with ages ranging from 33 to 45 years (average 38.1 ± 3.5 years). All experiments utilizing animals were approved by the Institutional Animal Care and Use Committee  of CHA University. The animals were handled in strict accordance with the institutional recommendations and best practices on the care and use of laboratory animals. All efforts were made to minimize suffering.scid/Ncrkoat female mice with severe combined immunodeficiency (SCID) were evaluated in all experiments: no uterine damage (Sham group), uterine damage with no PRP treatment (AS group), and uterine damage followed by PRP treatment (PRP-treated AS group). In AS mice (mice with AS induced by uterine damage) used for Experiments 1 and 2, uterine horn damage was induced bilaterally and human PRP was injected unilaterally (in the right horn) at 7 days after AS induction (uterine horn damage). Thus, data pertaining to AS mice from Experiments 1 and 2 were further stratified according to whether they were obtained for the PRP-treated AS horn (PRP-treated AS group) or for the untreated AS horn (AS group). In Experiment 3, some AS mice received bilateral uterine horn injury followed by bilateral PRP treatment (PRP-treated AS group) at 7 days after AS induction, whereas other AS mice received bilateral uterine horn injury with no PRP treatment (AS group). An overview of the study design is provided in Three experiments were conducted, each with a different purpose: Experiment 1 to assess endometrial regeneration , Experiment 2 to evaluate implantation outcomes at mid-gestation , and Experiment 3 to evaluate pregnancy outcomes . Three groups of 8-week old CB17 PrkdcPlatelet-rich plasma was used to observe the histological and molecular biological effects using animal models. Blood samples were obtained from six otherwise healthy female donors with AS, with no active infection. A 22 mL volume of whole blood was drawn from each donor using a syringe containing 3 mL of anticoagulant solution  and prepared using a PRS Bio Kit . The samples were centrifuged at 3,000 rpm for 5 min. After blood fractionation into three layers , the plasma and buffy coat were separated. A syringe was used to extract approximately 0.5 mL of plasma and 0.2 mL of buffy coat (platelets and leukocytes), obtaining 0.7 mL of PRP. Of the total PRP volume collected for each donor, 150 μL was sent to the laboratory to confirm the platelet concentration. Among the samples harvested from the six donors, the mean concentration of platelets was 232,200 cells/μL in the original sample and 1,871,000 cells/μL in the PRP.Prkdcscid/Ncrkoat female mice with SCID were housed in the Animal Care Facility of CHA University, under temperature- and light-controlled conditions (12-h light/dark cycle), and fed ad libitum. SCID mice were used for human PRP therapy on AS because they allow allogeneic and xenogeneic grafts. Eight-week-old mice provided by KOATECH  were used to establish an AS murine model according to a previously published protocol, with slight modifications  and evaluated for cellular and molecular signs of fibrosis and regeneration. Experiments included histological and immunofluorescence staining, as well as measurement of fibrosis marker expression levels.In Experiment 2, 10 mice were mated with healthy males at 14 days after experiment initiation (7 days after PRP treatment). On day 12 of pregnancy, the animals were sacrificed to evaluate the number and weight of IS.In Experiment 3, 16 mice were mated with healthy males at 14 days after experiment initiation (7 days after PRP treatment). While all AS mice received injury to the bilateral uterine horns, half received no PRP treatment, whereas the other half received PRP treatment to the bilateral horns. Pregnancy outcomes included the time to conceive, live-birth rate, and litter size.To investigate the endometrial structure, frozen uterine sections (12 μm) were fixed in 4% paraformaldehyde and stained with hematoxylin and eosin. The collagen areas were stained using Masson trichrome to evaluate fibrosis. Under Masson trichrome staining, the collagen fibers appeared stained in blue, the nuclei appeared stained in black, and the background appeared stained in red. The slides were examined using a suitable microscope .To determine the expression of COL1A1   after utCol1a1, Tgfβ1, Timp1). Uteri  were collected, immediately frozen in liquid nitrogen, and individually prepared for total RNA extraction. Total RNA was extracted from each uterine horn using Trizol Reagent  according to manufacturer’s instructions, and 2 μg of the extracted total RNA was subjected to RT using M-MLV reverse transcriptase  with random primers and oligo dT for cDNA synthesis. The synthesized cDNA was utilized for PCR with specific primers at optimized cycles. Subsequently, adequate primer pairs were used for PCR. Real-time RT-qPCR was performed by monitoring the increase in fluorescence of the SYBR Green dye  using a real-time PCR detection system . For between-sample comparison of transcript levels, a standard curve of cycle thresholds for several serial dilutions of a single cDNA sample was established and then used to calculate the relative abundance of each gene. The gene expression values were then normalized to the relative amounts of rPL7 cDNA (Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and real-time RT-qPCR analyses were performed to evaluate the level of RNA expression of fibrosis-related factors  was used for statistical analysis.All values represent means ± SD. Statistical analyses were performed using the Kruskal–Wallis one-way ANOVA test for more than two groups. Values of In Experiment 1 , the adeImmunofluorescence staining for COL1A1, a fibrosis-associated factor, was performed to evaluate the extent of fibrosis . The expCol1a1, Tgfβ1, and Timp1 was investigated using RT-qPCR and real-time RT-qPCR in Experiment 1 . These results indicate that human PRP infusion helps reduce the expression of fibrosis-related factors following endometrial injury.The expression of fibrosis-related factors including riment 1 . On RT-qp < 0.01), but no delay in embryo development was observed . These results indicate that implantation was impeded by endometrial injury but could be restored by PRP treatment, though not to pre-injury levels. While all Sham mice gave birth to live pups, AS mice did not give birth to any live pups (p < 0.01). Because AS mice failed to deliver, litter size could not be compared for this group (p < 0.01), PRP treatment clearly improved the rate of live-births since AS mice failed to deliver.In Experiment 3 , Sham miive pups , and mosis group . AlthougSeveral studies have suggested that PRP may be useful as an adjuvant treatment for endometrial injury . Howeverin vitro fertilization, and abnormal placentation  of the CHA Gangnam Medical Center for use of human PRP. The patients/participants provided their written informed consent to participate in this study. All experiments utilizing animals were approved by the IACUC of CHA University .JK and MP contributed to the experimental procedures, analysis and interpretation of data, drafting, and revision of the manuscript. JP and W-SL contributed to the data interpretation and revision of the manuscript. HS and SL contributed to the conception and design, analysis and interpretation of data, revision, and final approval of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


This article aims to provide guidance on prevention and treatment of COVID-19 in patients with genetic obesity. Key principals of the management of patients with genetic obesity during COVID-19 pandemic for patients that have contracted COVID-19 are to be aware of: possible adrenal insufficiency ; a more severe course in patients with concomitant immunodeficiency , although defective leptin signalling could also be protective against the pro-inflammatory phenotype of COVID-19; disease severity being masked by insufficient awareness of symptoms in syndromic obesity patients with intellectual deficit (in particular PWS); to adjust medication dose to increased body size, preferably use dosing in m2; the high risk of malnutrition in patients with Sars-Cov2 infection, even in case of obesity. Key principals of the obesity management during the pandemic are to strive for optimal obesity management and a healthy lifestyle within the possibilities of the regulations to prevent weight (re)gain and to address anxiety within consultations, since prevalence of anxiety for COVID-19 is underestimated. In the first half of 2020 there has been a rapid increase of patients diagnosed with a new disease, Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). On March 11, 2020, the World Health Organization declared COVID-19 a public health emergency of international concern. On 22-10-2020, 40,665,438 confirmed cases and 1,121,843 confirmed deaths were reported .The increased risk of a severe course of COVID-19 in obesity is particularly of great concern in subjects with severe obesity caused by monogenic disease or obesity syndromes, since the risk of a severe course of COVID-19 increases with increasing BMI . To dateIn the last three decades, increasing possibilities of genetic testing have led to the identification of various genetic causes of severe obesity. Genetic obesity (Orpha code: 77828) is a collective term for both monogenic and syndromic obesity. Genetic obesity disorders are severe and disabling disorders that form a heterogeneous group of conditions. They are classically divided into non-syndromic (Orpha code: 98267) and syndromic obesity (Orpha code: 240371). Non-syndromic genetic obesity disorders are often caused by a single gene defect leading to Leptin (LEP) deficiency, leptin receptor (LEPR) deficiency, pro-opiomelanocortin (POMC) deficiency, melanocortin 4 receptor (MC4R) deficiency or proprotein convertase subtilisin/kexint type 1 (PCSK1) deficiency. Recently, other variants of genes involved in or regulating the melanocortin pathway and leading to early and severe obesity such as MC4R regulatory protein, melanocortin receptor accessory protein 2 (MRAP2), adenylate cyclase 3 (ADCY3), steroid coreceptor activator-1 (SRC-1) or kinase suppressor of ras 2 (KSR2) , 11. LEPSyndromic genetic obesity differs from the non-syndromic diseases, as they have additional symptoms, apart from obesity –16, withIdentifying genetic obesity requires a structured approach and diagnosis is crucial, not only for optimal treatment of the accompanying symptoms such as visual and hearing impairment and endocrinopathies, but also because the obesity accompanying these diseases requires a tailored and life-long approach . For exaThis review will concentrate on those diseases and syndromes defined as non-syndromic and syndromic obesity by the orphanet classification system  and willSince the beginning of the COVID-19 pandemic, several risk factors for a severe course of the disease have been identified. Besides age  and malen = 265) treated at the intensive care unit at 6 University Hospitals in the USA have shown a significant inverse correlation between age and BMI. Indicating that younger patients, including some adolescents, had an increased risk of ICU admittance with increasing BMI when infected with COVID-19 [Furthermore, data from patients with a COVID-19 infection . Obesity is associated with an imbalance in the renin-angiotensin-aldosterone system. This imbalance is characterized by an overexpression of angiotensin 2 (ANG2). ANG2 can be converted to angiotensin 1–7 (Ang1–7) by Angiotensin converting enzyme (ACE2) . ANG2 haInflammatory dysregulation (often referred to as a cytokine storm) is an important driver of the more severe course of COVID-19 , 7, 37. Obesity is linked to further metabolic and other severe impairments, such as type 2 diabetes, hypertension, thrombogenic risk, and lung impairment. These conditions all decrease the ability to cope with COVID-19 .Viral shedding. The concept that patients with obesity might have increased viral shedding of SARS-CoV-2 comes from studies on the influenza A virus. It was found that obese patients are more contagious than lean patients. This is due to several factors. First, symptomatic obese patients shed influenza A virus 42% longer than lean patients, probably due to their altered immune response . Second,Vaccine effectiveness. An effective vaccine for SARS-CoV-2 is highly anticipated. However, individuals with obesity are known to have a decreased influenza vaccine effectiveness, probably due to alterations in the immune system . It is pLEP. Obesity is characterized by higher LEP and lower adiponectin concentrations. LEP is a pro-inflammatory adipokine, while adiponectin is an anti-inflammatory adipokine . In addiRespiratory dysfunction. Obesity is associated with pulmonary dysfunction, with increased airway resistance, impaired gas exchange and low lung volume and muscle strength. Furthermore, abdominal obesity leads to decreased diaphragmatic excursion . All theBariatric surgery (BS). Little is known about the post BS condition and COVID-19 but this aspect was assessed in a cohort of 738 patients albeit with common obesity who underwent BS in France. The prevalence of likely COVID-19 and its risk factors was evaluated and revealed that in patients followed-up after BS, the disease occurred in 8.4% of the patients among whom 6.4% had a severe form requiring hospitalization (1.6% died). While the number of likely infection by SARS-CoV-2 was apparently similar to the general population in a similar geographic area, the COVID-19 likely group had a higher proportion of persistent type 2 diabetes at the last follow-up and showed a higher percentage of weight loss since the bariatric intervention. In this group, severe forms of COVID-19 requiring hospitalization were associated with persistent type 2 diabetes. This illustrates the particular attention that must be paid to patients who have lost weight but with the persistence of type 2 diabetes in this pandemic context .There are several possible pathways that could explain why obesity per se is associated with a more severe course of COVID-19 infection. These plausible, but speculative, pathways are discussed shortly.In contrast to the extensive literature on obesity contributing to increased risk of a severe course of COVID-19 , literatSeverity of obesity. As mentioned above, this group of patients as a whole tends to have more severe obesity and the risk of a severe course of COVID-19 increases with increasing obesity class , 7, 27.Type 2 diabetes and hypertension. With increasing obesity class, there is an increasing risk of type 2 diabetes and hypertension, both independent risk factors for COVID-19 severity . The preRespiratory insufficiency. Sleep apnoea is associated with severe obesity. In PWS, risk on sleep apnoea and hypoventilation syndrome from central and obstructive origin is increased . ObstrucImpaired immune system is common in patients with LEP and LEPR deficiency. Of the total of 88 LEPR deficient patients that have been reported, 23 (52%) presented with frequent infections, of which 3 died due to infections in childhood. In addition, 2 (5%) had lowered CD4+ T-cell count with compensatory increased B-cell count. One patient (2%) had alterations in immune function . It has Adrenal insufficiency. Various genetic obesity disorders are associated with an increased risk of adrenal insufficiency, such as POMC deficiency , PCSK1 dThe risk of infection can be increased by behavioural issues. For instance, in patients with PWS, social distancing and face mask wearing can be difficult given the behavioural and intellectual problems these patients encounter.The presence of an intellectual disability can increase the difficulty of care management and care planning. They can have difficulties in expressing concerns or complaints. Especially in patients with PWS it is known that they can have a decreased sense of pain and fever can be absent even when severely ill .Hypogonadism. Genetic obesity is associated with hypogonadotropic hypogonadism. Both testosterone and oestradiol have proven anti-inflammatory, immunomodulatory and protective effect , 65. It While surgical weight-loss treatment might not be recommended in some forms of genetic obesity, some patients with these diseases underwent BS. There is no information on this specific group.Malnutrition. Obesity does not protect against malnutrition as has been recently reviewed . MoreoveTo identify possible risk factors of a more severe course of COVID-19 that are specific for patients with genetic obesity, there are a number of characteristics of these diseases that we need to consider.Although the majority of factors important for the treatment of patients with genetic obesity in the context of COVID-19 are addressed in the paragraphs above, there are still some additional considerations to discuss. First of all, the severely increased fat mass in most patients with monogenic and syndromic obesity should be taken into consideration when drugs are prescribed. Specifically, in treatment with fat soluble drugs such as glucocorticoids and certain antibiotics, dosing per metre squared should be considered over normal dosing regimens. In addition, considering the large amount of thromboembolic complications in COVID-19, we stress the importance of taking BMI into account when calculating the dose of prophylactic anticoagulants.Since the emergence of SARS-CoV-2, many governments have introduced partial or complete lockdown with various measures such as social distancing. Given the increased possibility of a severe course of COVID-19 in people with obesity, the question rises whether extra measures should be taken to prevent people with severe obesity, such as people with genetic obesity, from contracting the disease. On the other hand, the COVID-19 quarantine measures can be a health threat in itself, especially in children. Studies report adverse effects on psychological wellbeing such as anxiety, worrying, irritability, depressive symptoms and post-traumatic stress disorder symptoms in 19–44% of children from the general population , 71. In Also, quarantine measures have a considerable impact on lifestyle as observed in an Italian study showing unfavourable changes in eating, sleeping and activity behaviours in children and adolescents with obesity . Many pa2). Maintaining a healthy lifestyle by engaging in physical activity even indoors and making healthy food choices are strongly encouraged. Ongoing monitoring of genetic obesity is important to maintain. During quarantine or possible future lockdowns, maximum efforts should be undertaken to make sure that obesity treatment and check-ups are continued. The most important recommendations are summarized in Box In conclusion, although literature on COVID-19 and genetic obesity is lacking, there is a theoretical basis to assume that these patients have an increased risk for a severe course of COVID-19, especially in case of severe obesity . However defective LEP signalling could also be protective against the pro-inflammatory phenotype of COVID-19Be aware of disease severity being masked by insufficient awareness of symptoms in syndromic obesity patients with intellectual deficit (in particular PWS)2Adjust medication dose to increased body size, preferably use dosing in mBe aware of the high risk of malnutrition in patients with Sars-Cov2 infection, even in case of obesityObesity management during the pandemicStrive for optimal obesity management and a healthy lifestyle within the possibilities of the regulations to prevent weight (re)gainAddress anxiety within consultations, since prevalence of anxiety for COVID-19 is underestimatedPOMC pro-opiomelanocortin, PWS Prader-Willi Syndrome, LEP leptin, LEPR leptin receptorAbbreviations: Due to the emerging nature of the COVID-19 crisis, this document is not based on extensive systematic review or meta-analysis, but on literature review and expert consensus. The document should be considered as guidance only; it is not intended to determine an absolute standard of medical care. Healthcare staff need to consider individual circumstances when defining the management plan for a specific patient.


We evaluated whether using county-level data to characterize public health measures in cities biases the characterization of city populations. We compared 4 public health and sociodemographic measures in 447 US cities  to the same measures calculated for counties that contain those cities. We found substantial and highly variable city–county differences within and across metrics, which suggests that use of county data to proxy city measures could hamper accurate allocation of public health resources and appreciation of the urgency of public health needs in specific locales. Many local health departments develop city-level public health policies but lack city-level health data. This lack causes reliance on county-level data, which may misrepresent city populations.We found substantial and highly variable city–county differences within and across 4 public health metrics, suggesting use of county-level data may mischaracterize health metrics in cities.Use of county data to proxy city measures could hamper municipal public health policymaking. Public health officials concerned with cities should use city-level data whenever possible.When local officials develop and evaluate city health policies, they often cannot access city-specific health data, and instead rely on county data. Yet, a county’s characteristics may differ substantially from a city within it. Counties are usually larger than their cities, are mostly administered by different governmental entities, and contain overlapping, but distinct, populations, with different sociodemographic composition, health behaviors, and health conditions . As suchWe evaluated the potential for bias by comparing estimates of 4 public health measures, calculated by using data from the City Health Dashboard (4) for 447 cities and their corresponding counties.The City Health Dashboard (Dashboard) includes 497 US cities with a population of 66,000 or more, as of 2010, and to ensure all states were represented, 3 smaller cities  are included. The sample for the present analysis included the 447 Dashboard cities that are nested within their surrounding counties. Nested means that a minimum of 90% of the city population resides within the surrounding county, omitting the 53 cities that overlapped, or shared, county boundaries.We then selected 4 measures to compare across city–county pairs: percent of non-Hispanic Black population, percent of children living in poverty, cardiovascular disease (CVD) deaths per 100,000 population, and life expectancy at birth. Percent of non-Hispanic Black  and perchttps://www.cdc.gov/nchs/nvss/index.htm) using our standing Dashboard agreement, and county-level data were obtained from CDC’s WONDER (Wide-ranging Online Data for Epidemiologic Research) website (https://wonder.cdc.gov/). We defined CVD deaths using a standard group of ICD-10  codes  provides census tract-level, small area estimates of life expectancy at birth for the period 2010–2015. Using USALEEP, we produced aggregate city- and county-level life expectancy estimates by calculating tract population-weighted means. Life expectancy for 8 cities and 9 counties were not available from USALEEP.For this analysis, percent of non-Hispanic Black and percent of children living in poverty were separately calculated at the city- and county-level by using the US Census American Community Survey, 2017 5-Year Estimates (0) codes , with th0) codes . CDC’s NRelative and absolute percent differences were calculated to establish whether observed differences in metric estimates were meaningful or not. Consistent with previous literature, absolute differences greater than 5% and relative differences greater than 15% were considered meaningful . Last, wt-tests for city–county differences across all 4 measures yielded P values less than 0.01 . Paired han 0.01 . On averWe found substantial variations in city–-county differences: for all 4 metrics, the standard deviation of the city–county difference was larger than the mean of the difference. For example, poverty was on average 2.65% greater in cities than in the counties that contain them, but the standard deviation of the city–county difference for that measure was 9.65% . Both abEstimates for CVD mortality, the percent of non-Hispanic Black population, and the percent of children living in poverty were, on average, higher in cities than in counties, and most city–county pairs had meaningful absolute and relative differences for these 3 metrics. The higher percent of children living in poverty and non-Hispanic Black residents suggests that values of other health metrics may also be lower in cities than in counties that contain them, because both race and poverty are associated with health . HoweverAlthough the general tendency was toward underrepresentation of poorer health outcomes when county-level metrics were compared with city-level metrics, observed differences varied substantially. As key public health actors, cities’ reliance on county-level estimates could in some cases attenuate the apparent need for action and resources. Although these findings do not include cities with populations less than 66,000, smaller cities typically include smaller proportions of the containing county’s population, so cities with lower population counts may be subject to similar or more substantial city–county differences.Recent improvements in the ability of researchers to parse health-related data to specific geographic boundaries, and to generate modeled estimates when parsing is infeasible, have provided policy makers access to accurate city-level estimates, which were previously unavailable because of sparse data, methodologic limitations, or a lack of attention to city-level data. Such city-level data are increasingly publicly available from many sources, including the Dashboard. Cities’ use of granular city-level data should result in more accurately-targeted interventions and programs, which can contribute to better overall health outcomes.