As of 10/19/20

LitCovid

LitCovid is a database of research studies about COVID-19 published by The National Institutes of Health. It is considered to be the most comprehensive, up-to-date resource on COVID-19, providing access to a total of 61,346 studies (so far) in PubMed that is updated daily. The articles are categorized by eight research areas. They are also categorized by journal of publication and geographic area.

Research for providers can be found at Disaster Consult

Epidemiology & Transmission
Vaccine Development
Management
Foundational Articles

Date: 10/11/2020

Study Title: Comparison of Clinical Features of COVID-19 vs Seasonal Influenza A and B in US Children

Link: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/27702

Purpose: Compare clinical features between COVID-19 and influenza in children

Study Methods: This was a retrospective cohort study, meaning that data was collected on patients that were already admitted. It was conducted in Children’s Hospital in Washington, DC. Authors used data from patients collected data on flu patients between October of last year and June of this year and data on COVID-19 patients from March to May of this year.

Results

Who was included in the study?

  • 315 patient diagnosed with COVID-19 
  • 1402 patients diagnosed with seasonal influenza 
  • NO patients with co-infection were included

There was no statistically significant differences for the following outcomes: 

  • Hospitalization Rate 
  • Requiring ICU stay 
  • Patients Requiring Mechanical Ventilation 
  • Hospital length of stay 
  • Mechanical Ventilator Support 

Researchers noted the following differences in frequency of symptoms

Main Conclusions:

  • No statistically significant differences in hospitalization rate, ICU admission rate, or mechanical ventilator support 
  • More patients hospitalized with COVID-19 report certain clinical symptoms 
    • Rates similar to other studies 
  • Patients hospitalized with COVID more likely to be older 
  • After school closures, an abrupt decrease in influenza also occurred

Date: 09/29/2020

Study title: Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism Predominates in Choroid Plexus Epithelium

Link: https://reader.elsevier.com/reader/sd/pii/S193459092030463X?token=82D6CC8501F5971D4341438BE888BADDF49712CB1C0D2DFE91DACE8277ADBC6AD104EC42FF4434B430A0F7320A08F4CA 

Summary: This experimental study utilized wet-lab techniques to identify the choroid plexus of the brain as a major neurotropic target for COVID-19 infection. Moreover, the researchers determined brain cell death, brain cell function deficits, DNA dysregulation, and neuroinflammation as the major molecular mechanisms by which COVID-19 infection to the brain can cause neurological damage. 

Background: Many COVID-19 patients have reportedly experienced neurological symptoms, however little is known regarding the molecular mechanism by which the virus is able to infect and cause dysregulation of brain cells. The purpose of this study is to provide evidence for how COVID-19 is able to infect brain cells, and discuss hypothetical avenues for treatment of virus-induced neurological complications.  

Methods: The researchers first determined whether lab engineered stem cells derived from the brain and lab engineered organoids of various brain structures (cortex, hippocampus, hypothalamus, and the midbrain, choroid plexus) were vulnerable to COVID-19 infection. Then, they performed various fluorescent immunohistology staining protocols and statistical analyses to determine the mechanism of action by which the virus induced damage to the identified susceptible cells and structures.      

Results: The researchers discovered that the lab engineered stem cells derived from the brain and the choroid plexus organoids weresusceptible to COVID-19 infection. The choroid plexus are structures in the brain responsible for producing cerebrospinal fluid, a nutrient-rich fluid that surrounds, protects, nourishes, and filters waste from the brain and spinal cord. They further discovered that COVID-19 infection of the choroid plexus induces cell death and abnormal DNA expression that promotes neuroinflammation and other losses of brain cell function. 

Conclusion: Overall, the researchers discovered that the mechanism by which COVID-19 affects the neurological system is central. Specifically, they found that the virus infects the choroid plexus of the brain and leads to brain cell death, DNA expression dysregulation, and a neuroinflammatory response at the molecular level. More research needs to be done to determine whether and how these molecular changes translates to neurologic deficits. However, these findings provide valuable insight into possible therapeutic targets for treating COVID-19 induced neurological dysfunction (i.e. anti-inflammatory substances to combat the viral-induced neuroinflammatory response).

Title: Spectrum of the neuropsychiatric manifestations of COVID-19

Link: https://www.sciencedirect.com/science/article/pii/S0889159120310084?via%3Dihub

Background: This study used a large data set to determine common neuropsychiatric symptoms in patients that are positive with COVID-19

Methods

  • The authors used data on adults infected with COVID-19 from a demographic database of electronic health records called TriNetX
  • Data was collected from January 20, 2020 to June 10th, 2020
  • In total, data from 40,469 patients were included in the study
    • The majority of these patients (76%) were from the US and 74% were outpatient

Results

  • A total of 9086 (22.5%) of patients had neuropsychiatric manifestations
  • The most common psychiatric manifestations were:
    • Anxiety and related disorders (4.6%)
    • Mood disorders (3.8%)
    • Emotional state symptoms and signs (0.8%)
    • Suicide ideation (0.2%)
  • The most common neurological manifestations were:
    • Headache (3.7%)
    • Sleep disorders (3.4%)
    • Encephalopathy (2.3%)
    • Stroke & TIA (1.0%)
    • Seizure Disorder (0.6%)

Interpretation of Results 

Psychiatric Symptoms

  •  In regards to psychiatric symptoms, not much explanation was offered
  • Psychiatric symptoms are likely not just isolated to patients affected with COVID-19, but also healthcare workers taking care of patients

Interpretation of Neurological Symptoms: Proposed mechanisms of neuropsychiatric manifestations are broad and depend largely on the pathology

  • Headaches: Likely precipitated by diminished blood flow and oxygen to the brain
  • Stroke: Increased inflammation and coagulation (i.e. thickening of blood)  
  • Seizures: Decreased seizure threshold due to cytokine surge

Reference: Nalleballe, K., Onteddu, S. R., Sharma, R., Dandu, V., Brown, A., Jasti, M., … & Kapoor, N. (2020). Spectrum of neuropsychiatric manifestations in COVID-19. Brain, behavior, and immunity, 88, 71-74.

Date: 09/12/2020

Title: Prevalence of Depression Symptoms in US Adults Before and During the COVID-19 Pandemic

Link: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2770146

Background: The purpose of this study was to estimate the prevalence of depression symptoms and associated risk factors among US adults, before and during the COVID-19 pandemic.

Methods: This study used data from two nationally representative surveys of US adults 18 or older. The first one used was the National Health and Nutrition Examination Survey conducted from 2017 to 2018, which included a total of 5065 participants. The second one used was the Life Stressors Impact on Mental Health and Well-being study, conducted in early April of 2020, which included a total of 1441 participants. The Patient Health Questionnaire-9 was used to determine the degree of depressive symptoms, with the five categories of none, mild, moderate, moderately severe, and severe. 

Results: Analysis showed that prevalence of depressive symptoms was higher in every category during the COVID-19 pandemic compared with before

  • Mild: 21.8% prevalence during vs.16.2% before 
  • Moderate: 14.8% prevalence during vs. 5.7% before 
  • Moderately severe: 7.9% prevalence during vs. 2.1% before 
  • Severe: 5.1% prevalence during, 0.7% before 

Higher risk of depression symptoms were associated with the following risk factors: 

  • Having less than $5,000 in savings 
  • Household income of < $20,000
  • Marital status of widowed, separated, divorced, or neve married
  • Exposure to more COVID-19 related stressors, such as death of a loved one due to COVID-19 or loss of job 

Conclusion: Data indicated that the prevalence of depression symptoms in the US was more than 3 times higher during the COVID-19 pandemic compared with prior. This is compared to Risk factors for increased burden of depressive symptoms included lower income, stressors resulting from the pandemic (i.e. loss of loved one due to COVID-19, and lower social support. Monitoring the prevalence and monitoring these symptoms as the pandemic continues will prove crucial to mental health and social policy decisions. 

Title: Transmission of SARS‐CoV‐2 through breast milk and breastfeeding: a living systematic review 

Link:https://nyaspubs.onlinelibrary.wiley.com/doi/full/10.1111/nyas.14477 

Background: This systematic review sought to investigate whether breastmilk and breastfeeding is a risk factor for COVID-19 transmission from mother to child.

Methods: The authors identified 37 articles analyzing the association between breastmilk/breastfeeding and COVID-19 transmission from mother to child. From these 37 articles, 340 patient records were retrieved and represented pregnant women who gave birth to only one child during the pandemic. Of these 340 mothers, 77 reported to breast feeding and their breast milk samples had been analyzed. Moreover, the analyzed studies reported all lactating mothers wore face masks while breastfeeding. Some studies reported mothers having to share a post-delivery room with one other patient.   

Results: Of the 77 lactating mothers, 19 children tested COVID-19 positive via lab confirmation. Moreover, 68 of the 77 lactating mothers tested COVID-19 positive. Of these 68 women, 9 of them had breast milk that was analyzed and tested COVID-19 positive. Of those infants exposed to the virus positive breastmilk, 4 tested COVID-19 positive. 

Conclusion: Based on these results there is no conclusive evidence indicating breastfeeding and breast milk as risk factors for COVID-19 transmission from mother to child. The authors noted that many of the studies analyzed were case studies and cohort studies, which rank low on the evidence-based practice pyramid due to bias and other sources of error. Also, there was considerable variability in the methods between articles which can introduce error into results. Overall, more research needs to be conducted on this topic. 

Date: July 9, 2020

Title: Study Title: Persistent Symptoms in Patients After Acute COVID-19

Link: https://jamanetwork.com/journals/jama/fullarticle/2768351?resultClick=1

Background: 

  • Information is lacking on what symptoms persist after recovery 
  • Assessed persistant symtpoms in patients who were discharged from the hospital after recovery from COVID-19

Methods: 

  • Recovered COVID-19 patients were included 
  • Comprehensive medical assessment with a detailed history and physcial examination was performed 
  • Data on all clinical characteristics, including clinical and pharmacological history, lifestyle factors, vaccination status, and body measurements, were collected in a structured electronic data collection system.

Results: 

  • n=143; mean age was 56.6 years, and 37% were female 
  • During hospitalization 72.7% agad evidence of pneumonia; median length of hospital stay was 13.5 days; 21 patients (15%) received noninvasive ventilation and 7 patients (5%) received invasive ventilation.
  • Patients were assessed a mean of 60.3 days after the onset fo the first COVID-19 symptoms 
  • At time of initial evaluation only 12.6% were completely free of any COVID-19 related symptoms, while 32% had 1 or 2 symptoms and 55% had 3 or more.
  • None of the patients had fever or any signs or symptoms of acute illness.
  • Worsened quality of life was observed among 44.1% of patients. 
  • The Figure shows that a high proportion of individuals still reported fatigue (53.1%), dyspnea (43.4%), joint pain, (27.3%) and chest pain (21.7%).

Conclusions: 

  • This study found that in patients who had recovered from COVID-19, 87.4% reported persistence of at least 1 symptom, particularly fatigue and dyspnea. 
  • Limitations of the study include the lack of information on symptom history before acute COVID-19 illness and the lack of details on symptom severity.

Racial Disproportionality in Covid Clinical Trials 

https://www.nejm.org/doi/pdf/10.1056/NEJMp2021971?articleTools=true

Date: 8/14/2020

Background:

  • What is a perspective piece? A scientific-focused perspective piece presents an author’s viewpoint on a research topic, hypothesis, or scientific theory based on analysis of current and relevant literature. While opinions are generated and based on current scientific evidence, the opinions presented have no statistical significance and are not considered as hard scientific data.  
  • What is the purpose of a perspective piece? The purpose of a perspective piece is to highlight an important topic in which future true scientific research/assessment is warranted for the betterment of society.

Current literature provides scientific backing to support the observation that higher rates of Covid-19 infection, hospitalization, and deaths are occurring within racial and ethnic minority communities due to long-existing systemic health care disparities. There is currently no data addressing how host biologic and genetic factors influence Covid-19 outcomes. However, the health community does know that racial and ethnic minorities are at higher risk for certain chronic conditions (i.e. diabetes, obesity, hypertension, and other cardiopulmonary issues) that are known to place individuals in a high-risk group if infected with Covid-19. In light of this health inequity, this NEJM perspective piece seeks to highlight the observation that there is underrepresentation of ethnic and racial minority groups in Covid clinical trials being conducted in the United States.   

 Scientific findings which the author’s viewpoint are based upon: 

  • The current standard of care treatment for Covid-19 in the United States is the antiviral medication called remdesivir. While the preliminary results from the remdesivir clinical trials (the National Institute of Allergy and Infectious Diseases (NIAID) Adaptive Covid-19 Treatment Trial) were extracted from a small data set, the authors observed the following:

o  Only 20% of the 1,063 patients randomly assigned the placebo were African American 

o  Only 11% of the 397 patients randomly assigned remdesivir were African American 

o  Data on race and ethnicity was not even collected for 53 of the 397 patients randomly assigned remdesivir  

o  Communities in which trials were conducted reported an overrepresentation of African American, Latinx, and Native American populations suffering from of who passed away du to Covid-19. However, data samples for the clinical trials reflected a gross underrepresentation of these minority groups.

Conclusion:The authors speculate that the lack of diversity in the NIAID remdesivir clinical trials could have been due to: deeply rooted medical distrust by minority communities towards the healthcare system; financial barriers; transportation barriers; poor health literacy; language barriers; and selection bias stemming from implicit biases against minority groups by principal investigators. It is imperative that future Covid-19 clinical and vaccine trials make an effort to ensure appropriate representation of all minority groups as long as there is no data to support that differences in race and ethnicity do not influence Covid-19 outcomes. 

Date: 08/06/20

A systematic review and meta‐analysis of children with Coronavirus Disease 2019 (COVID‐19)

https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.26398

Background: Much is known about how COVID-19 presents in the adult population, however there is still a lot to learn in terms of how the virus affects children. The purpose of this study is to clearly characterize illness classifications, clinical symptoms, laboratory findings, and radiology findings in the COVID-19 pediatric population.   

Methods: A meta-analysis was conducted in which 48 pediatric studies on COVID-19 between December 25th, 2019 and April 30th, 2020 were analyzed. In total, 5,829 pediatric patients were assessed for common illness classifications, clinical symptoms, laboratory findings, and radiology findings. 

Results: 

  • Illness classifications
    • 51% moderate illness
    • 33% mild illness
    • 20% asymptomatic 
    • 14% of cases were classified as “critical” in child under 1-year old
  • Clinical symptoms
    • 51% fever
    • 41% dry cough 
    • 33% vomiting was found in child under 1-year old
  • Laboratory findings
    • 69% normal white blood cell count
    • 16% lymphopenia (an abnormally low lymphocyte count in the blood)
    • 37% elevated creatine-kinase MB (typically elevated in the setting of cardiac issues) 
  • Radiology findings
    • 41% normal imaging 
    • 36% lung lesions (ground-glass opacities) on chest-CT 

Conclusion: The results of this study suggests that COVID-19 can affect children of all ages, and will most commonly present as a mild illness with fever, dry cough and rarely lymphopenia. Moreover, critical illness and vomiting are red flags in babies under 1-year old that warrants COVID-19 evaluation. This study is useful in terms of beginning to define the impact of COVID-19 in children, and can be helpful in creating a more robust epidemiological case definition. However, despite the results of this study, further research needs to be conducted to evaluate the clinical presentation of COVID-19 in the pediatric population.

Date: July 27, 2020

Study Title: Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19)

Link: https://jamanetwork.com/journals/jamacardiology/fullarticle/2768916

Background: 

  • There remains poor insight into the cardiovascular sequalae in recovered COVID-19 patients, especially for those with no preexisting conditions, who were not hospitalized, or had no or only mild symptoms

Methods: 

  • n=100 
  • Prospective observational cohort study 
  • Participants had recently recovered from COVID-19 infection between April and June 2020
  • Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained for each participant. 
  • Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor–matched patients (n = 57).

Results: 

  • 53% Male, average age 49 years old
  • Of the 100 patients who recovered from COVID-19, 67 (67%) recovered at home, while 33% required hospitalization
  • At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (3 pg/mL or greater) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (13.9 pg/mL or greater) in 5 patients (5%).
  • Compared with healthy controls and risk factor–matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, higher left ventricle mass, and raised native T1 and T2 (all worse outcomes) 
  • A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings

Conclusions: 

  • Cardiac imaging revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis. 
  • These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.

Date: 8/01/20

Effect of moist heat reprocessing of N95 respirators on SARS-CoV-2 inactivation and respirator function 

Link: https://www.cmaj.ca/content/cmaj/early/2020/07/30/cmaj.201203.full.pdf

Brief Summary: This experimental study tests the effectiveness of an affordable, rapid, and regulatory compliant thermal decontamination protocol of N95 respirators. N95 respirator masks were inoculated with either the SARS-CoV2 virus or E. Coli bacteria, and infectious disease inactivation and mask structural integrity were assessed post thermal disinfection protocol under controlled conditions. The researchers present an effective thermal disinfection protocol for N-95 respirator masks that successfully leads to viral inactivation of SARS-CoV2 while maintaining mask structural integrity for up to 10 disinfection cycles.

Background: COVID-19 cases are still overwhelming many healthcare facilities around the world, and with that continues the healthcare supply shortage. Notably, there is constant worry over PPE shortages. Consequently, many healthcare workers are left with no choice but to reuse N95 masks, which is an important piece of PPE as the COVID-19 virus is transmitted primarily via respiratory droplets. The purpose of this research article was to test the effectiveness of an affordable, rapid, and regulatory compliant thermal decontamination protocol of N95 respirators. This experiment was United States National Institute for Occupational Safety and Health compliant.    

Methods: 

  •  Experimental variable: 4 N95 respirator masks were inoculated with the SARS-CoV2 virus 
  • Control variable: 4 N95 respirator masks were inoculated with E. Coli 
  • Viral inactivation was assessed post a 60-minute disinfection procedure under controlled environmental conditions (70 degrees C and 0% relative humidity)
  • Multiple cycles of the thermal disinfection protocol was performed on masked subjects
    • Structural integrity of the N-95 respirator masks was assessed via electron microscopy for particle filtration efficiency, breathing resistance, respirator/mask fit 

Results: 

  • 1 cycle of the thermal disinfection protocol led to SARS-CoV2 inactivation in all 4 inoculated mask samples
  • Masks inoculated with E. Coli and treated with the thermal disinfection protocol at 70 degrees C with 50% relative humidity became sterilized, as compared to untreated mask samples that remained contaminated. However, the thermal disinfection protocol failed to result in full decontamination below a relative humidity of 50%.  
  • N-95 respirator masks maintained structural integrity and showed effective particle filtration efficiency, breathing resistance, respirator/mask fit after 10 thermal disinfection cycles. 

Conclusion: Based on the results, the researchers present an effective thermal disinfection protocol for N-95 respirator masks that successfully leads to viral inactivation of SARS-CoV2 while maintaining mask structural integrity for up to 10 disinfection cycles. This protocol can be implemented in healthcare facilities to help reduce the N-95 mask shortage supply burden while also ensuring the safety of healthcare workers treating COVID-19 patients. 

Study Title: Persistent Symptoms in Patients After Acute COVID-19

Link: https://jamanetwork.com/journals/jama/fullarticle/2768351?resultClick=1

Background: The symptoms associated with COVID-19 infection are well documented (cough, fever, dyspnea, musculoskeletal symptoms such as myalgia, joint pain, fatigue, gastrointestinal symptoms, and loss of taste or smell). However, information is lacking on symptoms that persist after recovery. This study assessed persistent symptoms in patients who were discharged from the hospital after recovery from COVID-19.

Methods: 

  • Those included were those who were previously hospitalized from COVID-19 and have now met the WHO criteria for discontinuation of quarantine (2 negative COVID-19 tests 24 hours apart, no fever for 3 consecutive days, improvement in other symptoms).
  • Data on specific symptoms potentially correlated with COVID-19 were obtained using standardized questionnaires administered at enrollment. 
  • Patients were asked to retrospectively recount the presence or absence of symptoms during the acute phase of COVID-19 and whether each symptom persisted at the time of visit.
  • A visual analog scale was used to ask patients to score their quality of life from 0 (worst imaginable health) to 100 (best imaginable health) before COVID-19 and at the time of visit. A difference of 10 points defined worsened quality of life.

Results:

  • Total sample size was 143, mean age was 56.5 years old (range 19-84), and 37% female.
  • 72.7% of participants had evidence of pneumonia, 15% received noninvasive ventilation, 5% received invasive ventilation
  • Patients were assessed a mean of 60.3 days after the onset of the first COVID-19 symptom.
  • Worsened quality of life was observed among 44.1% of patients
  • Most frequently persisting symptoms: fatigue (53.1%), dyspnea – shortness of breath (43.4%), joint pain (27.3%), and chest pain (21.7%)

COVID-19 persisting symptoms after meeting WHO criteria for discontinuation of quarantine (2 negative COVID-19 tests 24 hours apart, no fever for 3 consecutive days, improvement in other symptoms). None of the patients had fever or any signs or symptoms of acute illness. 


Percentage of study population
Free of COVID-19 related symptom1 or 2 symptoms3+ symptoms
12.6% 32%55%

Conclusion: 

  • 87.4% of participants had at least 1 symptom, most commonly fatigue and dyspnea (shortness of breath).
  •  Limitations: single center study, small sample size
  • Patients with community-acquired pneumonia can also have persistent symptoms, suggesting these findings may not be exclusive to COVID-19.
  • Clinicians and researchers have focused on the acute phase of COVID-19, but continued monitoring after discharge for long-lasting effects is needed.

Study Title: Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality

Link: https://jamanetwork.com/journals/jama/fullarticle/2767669?resultClick=1

Background: ACE inhibitors and ARBs are frequently used to treat hypertension and heart conditions. This study attempts to find any associations with greater susceptibility to COVID-19 and/or worse outcomes with COVID-19 for those on ACE inhibitors or ARBs. Interest has been directed to the use of ACEIs/ARBs because these drugs may affect the ability of SARS-CoV-2 to infect cells through upregulation of angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2 cell entry. Based on this suggested mechanism, media reports have raised questions about ACEI/ARB treatment in the setting of COVID-19. 

Methods: Using the Danish national administrative registries, the authors examined outcomes for patients with COVID-19 between February 22 to May 4, 2020. ACE inhibitors and ARB use is defined as prescription fillings 6 months prior to infection.

For the retrospective cohort study, there were 3 outcomes of interest compared by ACEI/ARB use or no use. The primary outcome was all-cause death. Secondary outcomes were (1) a composite of death or severe COVID-19 and (2) severe COVID-19. Patients were followed up from the index date and until 1 of the following: outcome occurrence, end of study period (May 4, 2020), or emigration from Denmark.

Results:

  • In a retrospective cohort study of 4480 patients diagnosed as having COVID-19, prior ACEI/ARB use, compared with no use, was not significantly associated with mortality 
  • In a study on patients with hypertension, use of ACEI/ARB, compared with use of other antihypertensive medications, was not significantly associated with COVID-19 diagnosis

Conclusion: 

  • Prior use of ACEI/ARB was not significantly associated with COVID-19 diagnosis or with mortality among patients diagnosed as having COVID-19.
  • This was an observational study; no causal inference can be made and relationships should be interpreted as associations.
  • Prior use of ACEI/ARBs was not significantly associated with COVID-19 diagnosis among patients with hypertension or with mortality or severe disease among patients diagnosed as having COVID-19. 
  • These findings do not support discontinuation of ACEI/ARB medications that are clinically indicated in the context of the COVID-19 pandemic.

Hospitalization and Mortality among Black Patients and White Patients with Covid-19

https://www.nejm.org/doi/pdf/10.1056/NEJMsa2011686?articleTools=true

Brief Summary: The purpose of this retrospective cohort study was to identify and characterize differences in health outcomes, including hospitalization and in-hospital mortality outcomes, among 3,481 black and white patients infected with Covid-19 at an integrated-delivery health system in Louisiana. The researchers reported black patients exhibit higher rates of socioeconomic disparities and co-morbid conditions known to exacerbate Covid-19 infection. However, results indicate little disparities in terms of quality of care based on race.   


Background: Current epidemiological studies on Covid-19 have characterized the viral illness as affecting individuals of all sexes, ages and health statuses, with those 65 and older and those with chronic cardiovascular, pulmonary, and metabolic co-morbidities classified as most high-risk. However, data about racial- and ethnic- specific differences in health outcomes due to Covid-19 is lacking and requires research. Thus, the purpose of this retrospective cohort study was to identify and characterize differences in health outcomes, including hospitalization and in-hospital mortality outcomes, among black and white patients infected with Covid-19 at a healthcare system in Louisiana.   

Methods: The cohort population consisted of 3,481 Covid-19 positive patients seen within an integrated-delivery health system in Louisiana between March 1stand April 11th2020, among whom 60% were female, 70.4% were black non-Hispanic, and 29.6% were white non-Hispanic. All patients tested positive for Covid-19 via qualitative PCR assay. Hospitalization and in-hospital mortality outcomes were assessed between white and black patients. 


Results:

  • The % of black patients with Medicaid insurance was 3X as high as the % of white patients
  • Black patients were 2X more likely to live in low-income areas as compared to white patients 
  • Black patients had a higher prevalence of obesity, diabetes, hypertension, and chronic kidney disease than white patients 
  • Average length of hospital stay was similar for black and white patients

Conclusion:  Within an integrated-delivery health system in Louisiana with a 31% black patient population, an overwhelming majority of patients hospitalized with Covid-19 (76.9%) and those who passed (70.6%) from the viral illness are/were black. Moreover, statistical analysis suggests black and white patients experience similar in-hospital mortality outcomes even when adjusted for sociodemographic and clinical factors. Based on this data, it is evident that racially-driven health disparities within certain but not all areas of the healthcare system exist, and more research needs to be done to further evaluate and resolve such differences in health outcomes. 

Study Title: SARS-CoV-2 Positive Rate for Latinos in the Baltimore-Washington, DC Region

https://jamanetwork.com/journals/jama/fullarticle/2767632

Brief Summary: Data from the Baltimore and Washington DC region estimated that the overall SARS-CoV2 positivity rate among Latinos is over 40%, higher than any other ethnicity. Latino patients were more likely to be younger, male, and have no underlying health conditions compared to other ethnicities. Researchers suggest that this disparity may be partially explained by higher proportions of Latinos working in essential jobs and living in more densely packed housing.  

Background: Research data has indicated that people of African and Latino origins are disproportionately affected by COVID-19. This study analyzed trends in positivity rates for patients with SARS-CoV2 in the Baltimore/Washington DC region by race and ethnicity.  

Methods: Authors collected samples between March 11, 2020 and May 25, 2020 from 5 hospitals and 30 outpatient clinics that are part of the Johns Hopkins Health System. Samples were collected using nasopharyngeal swabs then analyzed using a precise DNA analyzing technique called reverse transcriptase-polymerase chain reaction (RT-PCR). Patients were asked to report self-identified race/ethnicity and were classified as Latino, Black, White, or Other which includes Asian American and Native Americans).

Results

  • The overall positivity rate for SARS-CoV-2 was 16.3% (6162 positive cases out of 37727 tested)
  • Overall and daily positivity rate by race/ethnicity distribution was as follows:

  • As testing volume increased, the overall positivity rate decreased
  • Overall, 35.9% of patients who tested were admitted to a hospital. The admission rate by ethnicity was as follows:  
    •  Latinos: 29.1%
    •  Whites: 40.1%
    •  Blacks: 41.7%
  • Compared to black and white patients, hospitalized Latino patients were younger, more likely to be male, and had lower rates of underlying conditions such as hypertension and COPD

Conclusions: At over 40%, Latinos in the Baltimore-Washington DC metropolitan area were much more likely to test positive for SARS-CoV-2 compared to other ethnic/racial groups. Researchers hypothesized that higher rates of essential worker status and decreased opportunities for social distancing due to densely populated housing among Latinos may contribute to this trend. Addressing the increased prevalence in the Latino community is critical in alleviating healthcare disparities and decreasing the spread of COVID-19 infection. 

Study Title: Clinical Impact of COVID-19 on patients with cancer (CCC19): a cohort study

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31187-9/fulltext

Brief Summary: This study examined cohort data from 928 patients with cancer. They noted the overall mortality rate of these patients was 13%. Risk factors for increased mortality included older age, having 2 or more underlying health conditions, active cancer, being male. 

Background: This study aimed to describe the outcomes of SARS-CoV2 positive cancer patients and identify prognostic factors for severe illness and mortality

Method: The researchers collected data on patients age 18 years and older with confirmed SARS-CoV2 and cancer using data from the COVID-19 and Cancer Consortium (CCC19) database. Patient data is from the USA, Canada, and Spain and was added between March 17 and April 16, 2020. Data was collected on a variety of factors including medications, other baseline clinical conditions, and treatment. The primary end datapoint used for the study is all-cause mortality within 30 days of COVID-19 diagnosis.

Results

A total of 928 patients were included for the study

  • The median age of these patients was 66 years with 30% of them aged 75 or older
  • 50% of the patients included were male and the other 50% female
  • At analysis of data, 13% of patients had died 

A total of 20 cancers were represented. The five most common cancers among patients were:

The following risk factors were associated with increased mortality after partial adjustment of variables:

  • Increased age
  • Male sex
  • Smoking status
  • Having two or more comorbidities
  • Active cancer
  • Treatment with azithromycin and hydroxychloroquine

Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments.

Interpretation: Cancer patients with COVID-19 have a relatively high 30-day mortality. Both general risk factors, such as higher number of comorbidities, and ones specific to cancer, such as active cancer, contribute to increased mortality. Longer term studies with larger sample sizes are needed to further understand the effects of SARS-CoV-2 on cancer.

Study Title: Association Between Mode of Delivery Among Pregnant Women With COVID-19 and Maternal and Neonatal Outcomes in Spain

https://jamanetwork.com/journals/jama/fullarticle/2767206?appId=scweb

Brief Summary: Early data from China reported severe complications in 8% of women with a confirmed COVID-19  infection. When considering these findings, it is important to note China has a higher rate of c-sections (>90%), compared to other parts of the world. This study sought to assess if mode of childbirth delivery holds an association to COVID-19 maternal complications. 

Methods: In this study, 82 women with singleton pregnancies and a positive COVID-19 test between March 12, 2020 and April 6, 2020 who delivered within the next 14 days of the positive test in Spain were included. Mothers were stratified by symptom severity at admission as: asymptomatic, mild, or severe (need for advanced oxygen support,  admission to ICU, or any signs of sepsis). Clinical deterioration was defined by an increased need for oxygen after delivery. 

Results: 

Table 1. Type of birth.

Type of InfectionCesarean DeliveryVaginal 
Severe4 (100%) (all C-sections in this category were due to COVID-19 infection)0 (0%)
None or mild COVID-19 symptoms37 (47%) (29 of which were for obstetrical indications and 8 for COVID-19 symptoms without other obstetrical indications)41 (53%) 

Table 2. Outcomes by delivery type.

OutcomeCesarean DeliveryVaginalClinical significance
Clinical FindingsMore likely to be obese, require oxygen at admission, and have abnormal chest x-ray n/aYes
Severe adverse outcomes (requiring ICU admission)5 (13.5%)0 (0%)Yes
Clinical deterioration after birth (after adjusting for potentially confounding factors)8 (21.6%)2 (4.9%)Yes 

Conclusions: 

  • Women undergoing cesarean delivery may have been at higher risk of adverse outcomes, but after adjusting for confounding factors, cesarean birth remained independently associated with an increased risk of clinical deterioration. 
  • The physiological stress caused by surgery is known to increase postpartum maternal complications and may be the reason for the clinical deterioration.

Psychological Distress and Loneliness Reported by US Adults in 2018 and April 2020

https://jamanetwork.com/journals/jama/fullarticle/2766941

Brief Summary: Data from this study suggests that US adults, on average, have experienced greater psychological distress  during the pandemic compared to 2 years ago. Certain groups, including young, poor, and Hispanic adults, face a disproportionately high burden of psychological distress. This increased prevalence may transfer to long-term psychiatric disorders. 

Background: The COVID-19 pandemic has introduced a variety of stressors to mental health including social isolation, economic strain, and anxiety about contracting the disease and the future. The researchers of this study sought to compare survey data in US adults from April 2020 with national data from 2018.  

Methods: Researchers from Johns Hopkins collected survey data from 1,468 adults aged 18 or greater from April 7-13 designed to be representative of US demographics. This was compared with data from 25,417 adults aged 18 years or older collected from the National Health Interview Survey from 2018. Data was collected using the Kessler 6 Psychological Distress Scale, with scores 13 or greater indicating serious levels of psychological distress.

Key Results: 

  • In April 2020, 13.6% of US adults reported symptoms of serious psychological distress, compared to 3.9% of adults in 2018 
  • Levels of psychological distress were most prevalent in the following socioeconomic groups 
    • Young adults age 18 to 29 years: 24% in 2020 vs. 3.7% in 2018
    • Adults with household incomes < $35,000/years: 19.3% in 2020 vs. 7.9% in 2018
    • Hispanic adults: 18.3% in 2020 vs. 4.4% in 2018 . 
  • All survey data is described in the following chart: 

Conclusions: This research indicates that the prevalence of psychological distress has increased since 2020. The Kessler 6 scale used to create the survey for the study has demonstrated accurate prediction of long-term mental illness. Thus, the distress experienced by US adults may transfer to long-term psychiatric disorders. Limitations of the study include different methods between the surveys to sample, recruit, and administer the two surveys as well as selection bias in response rates between the two surveys.  

Reduction of secondary transmission of SARS-CoV-2 in households by face mask use, disinfection and social distancing: a cohort study in Beijing, China 

https://gh.bmj.com/content/bmjgh/5/5/e002794.full.pdf

Brief Summary: As stay at home orders are gradually lifted and as more people brave public spaces, there is simultaneous public fear of contracting and/or potentially bringing COVID-19 home. Also, for those sharing a living space with an infected relative or friend, there exists uncertainty for how to protect oneself at home. This retrospective cohort study assessed predictors and rate of secondary transmission in COVID-19 positive households, and found that routine disinfectant hygiene practices, social distancing and mask wearing are effective in risk reduction of secondary transmission.

Background:Transmission of COVID-19 in communities and within families primarily occurs through close person-to-person contact and after touching an infected surface then subsequently touching one’s mouth and nose. While many agencies and political leaders have encouraged and even mandated community mask wearing, hand washing and social distancing, there is little information on how families can reduce risk of exposure within their households. The purpose of this study is to offer guidance and support for addressing how to limit risk of COVID-19 transmission within families.  

Methods:This retrospective cohort study conducted in Beijing, China evaluated the attack rate of secondary transmission in 335 people representing 124 families in which at least one family member was COVID-19 positive between Feb 28 to March 27, 2020. In addition, severity and characteristics of the primary COVID-19 cases and hygiene routines of all family contacts with primary cases were assessed as predictors of secondary transmission.  

Key Results: 

  • 23% secondary attack rate
  • 79% reduced transmission with mask use solely by primary case during viral incubation period (i.e. the period post infection and prior to symptom onset)
  • 77% reduction in transmission with daily use of chlorine/ethanol based disinfectant on household surfaces
  • 18-fold increased risk of transmission due to daily close contact with primary case
  • 22-fold increased risk of transmission if primary case experienced diarrhea 

Conclusion: Based on the results, the researchers provide evidence that mask use by infected persons during the highly contagious viral incubation period is significantly effective in reducing secondary transmission. Moreover, the data provides evidence to support avid use of routine disinfectant hygiene practices, social distancing and mask wearing as highly effective cautionary measures for reducing risk of COVID-19 transmission within at-risk family households.

Study Title: Epidemiology of COVID-19 Among Children in China

https://pediatrics.aappublications.org/content/early/2020/03/16/peds.2020-0702.1.long

Brief Summary: The researchers sought to characterize the clinical characteristics of pediatric patients with COVID-19 in China. On average, children experienced less severe symptoms compared to adult patients. However, it is important to note infants are particularly susceptible and vulnerable to infection. 

Background: This study aimed to describe demographics and epidemiological data on 2135 pediatric patients with COVID-19 in China. 

Methods: 2135 pediatric cases were evaluated through February 8, 2020 that were reported to the Chinese CDC. Children were defined as being <18 years old. The severity of COVID-19 was defined as the basis of clinical features, laboratory testing, and chest radiograph imaging, including asymptomatic infection, or as mild, moderate, severe, or critical. 

Results: Authors determined and presented the following descriptive characteristics among suspected and laboratory confirmed cases:

  • Median age: 7 
  • Case fatality rate: only 1 child died of the 2135 cases evaluated → 0.04% fatality rate
  • Few cases are severe and critical (5.8%) vs adults (18.5%)
  • Distribution of illness severity was as follows (n%):

Conclusions: 

  • Person to person transmission: Because most of these children were likely to expose themselves to family members and/or other children with COVID-19 this study supports person-to-person transmission 
  • Low case fatality rate, especially compared to adults 
  • Most cases are mild 
  • Compared to adults, pediatric manifestations of children’s COVID-19 may be less severe

Severe COVID-19 in Children and Young Adults in the Washington, DC Metropolitan Region

https://www.jpeds.com/article/S0022-3476(20)30581-3/fulltext

Brief Summary: In a sample of 177 pediatric patients in the DMV area with SARS-CoV2, approximately 76% of them presented with respiratory symptoms (i.e. cough, shortness of breath. About 25% of these 177 patients required hospitalization, with 5% specifically going to the intensive care unit. Hospitalized patients were significantly more likely to have an underlying health condition. 

Background: This paper aimed to describe clinical characteristics of pediatric patients admitted to Children’s National Hospital, the largest pediatric hospital in the DMV area.

Methods: This was an observational, retrospective cohort study. A total of 177 children and young adults with confirmed SARS-CoV-2 infected were included.These patients were treated at Children’s National Hospital between March 15 and April 30, 2020.

Key Results: Data showed the following age distribution of cases by severity of illness:  

Other important results included: 

  • Overall, 44/177 (25%) of patients infected with SARS-CoV2 required hospitalization
    • 9/44 (20%) of these patients were critically ill 
    • At the time of publication, there were no reported fatalities
  • 9.8% (177/1804) of symptomatic children and young adults tested were positive for SARS-CoV2
  • Approximately 76% (134/177) patients presents with respiratory symptoms (i.e. cough, shortness of breath) 
  • Patients >15 years were over-represented among critically ill cases 
  • 39% of patients positive for SARS-CoV2 had an underlying health condition
    • These patients were more likely to hospitalized (63% vs. 32%) 

Factors Associated With Mental Health Outcomes Among Health Care Workers Exposed to Coronavirus Disease 2019

Study link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090843/#!po=43.1818

Brief Summary: Healthcare workers often experience increased mental health burden when working during a disaster (i.e. pandemic). This survey study in China found that mild to severe levels of depression, anxiety, insomnia, and distress were fairly common among healthcare workers. This suggests that healthcare workers may need psychological support during a pandemic. 

Background: This study is a cross-sectional survey that aims to describe the prevalence and severity of depression, anxiety, insomnia, and distress among Chinese healthcare workers (i.e. nurses and doctors). It also looked at risk factors for developing these symptoms. 

Methods: Survey data was collected  on 1257 workers in 34 hospitals from January 29, 2020, to February 3, 2020, in China. Health care workers with hospitals that had wards or fever clinics for patients with COVID-19 were eligible. Specific surveys were created to assess for the symptoms, such as the 9-item patient health questionnaire that assesses for depression. 

Key Results: The data below shows the prevalence and severity of symptoms among providers 

Risk factors associated with increased risk of psychiatric symptoms were:

  • Being a frontline healthcare worker directly engaged in the treatment and care of COVID-19 patients 
  • Being a nurse
  • Being female 
  • Working in Wuhan (where the outbreak started)

Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2766037

Brief Summary: The most critically ill COVID-19 pediatric patients are admitted to pediatric intensive care units (PICUs). In this study conducted in the US and Canada, the vast majority of these patients had underlying health conditions (i.e. cancer, obesity). The majority were discharged from the hospital alive with only a small minority ultimately died. 

Background: This cross-sectional study aims to describe patients admitted to PICUs in the United States and Canada. It focused specifically on severity of disease, comorbidities (underlying health conditions), and early outcomes of these patients. 

Methods: The authors performed a retrospective review of medical records of 46 patients admitted to North American PICUs with confirmed COVID-19. These patients were admitted between March 14 and April 3, 2020, and follow-up of outcomes (i.e. discharge, death) was done through April 10, 2020.

Key Results 

  • Of the 46 hospitals, only 35% had at least one COVID-19 related admission to the PICU 
    • All of these hospitals were in the United States 
  • The median length of stay in the PICU was 5 days 
  • 83% of patients has significant preexisting comorbidities 
  • The outcomes at follow-up were as follows: 
    • Discharged: 65%
    • Died: 4%
    • Still hospitalized
      • Severe/critical condition: 19%
      • Mild or moderate condition: 13% 

Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area

https://jamanetwork.com/journals/jama/fullarticle/2765184

Brief Summary: The NYC region has been the epicenter of the COVID-19 pandemic in the United States. An analysis of 5700 patients with COVID-19 showed that older age, male gender, and the presence of a comorbidity (underlying health condition) are associated with hospital admission. Age over 65 and male gender were significant risk factors associated with death. 

Background: This study aims to describe the demographics, comorbidities, and outcomes of hospitalized patients with COVID-19 from a series of hospitals in the New York City area. 

Methods: Data was collected from hospitals from Northwell Health, the largest academic health system in New York. Data on 5700 hospitalized patients with laboratory-confirmed COVID-19 were included. Information on demographics, comorbidities, and laboratory data were extracted from medical records. 

Key Results

  • The median age of admitted patients was 63 years 
  • The majority (60.3%) of patients were male 
  • The average length of hospital stay of all patients was 4.1 days
    • This varied widely depending on severity of condition 
  • 88% of patients (4991) had more than one comorbidity
    • The median number of comorbidities was 4
    • The most common ones were hypertension (56.6%), obesity (41.7%), and diabetes (33.8%) 
  • Of the patients that died or were discharged, 14.2% were treated in the intensive care unit (ICU)
    • The median age of these patients was 68 years 
  • Age over 65 and male gender were determined to be risk factors associated with death 
    • A breakdown of age and mortality rate can be found at table 4 in the study 

Study Title: Coronavirus Disease 2019 in Children — United States, February 12–April 2, 2020

https://www.cdc.gov/mmwr/volumes/69/wr/mm6914e4.htm

Brief Summary: Early data from the Centers for Disease Control and Prevention (CDC) suggests that COVID-19 is less common in children compared to adults. Like adults, they typically present with one of the three symptoms of cough, fever, or shortness of breath. Certain conditions, such as asthma and HIV, may increase the severity of COVID-19 in children. 

Background: This study by the CDC aimed to describe the prevalence, common symptoms, and comorbidities associated with COVID-19 cases in patients <18 years. 

Methods: Data on COVID-19 cases were reported from 50 states, the District of Columbia, and four U.S. territories. Cases occurred during February 12- April 2, 2020. In total, 2572 cases in patients <18 years were reported.   

Results 

  • Overall, COVID-19 is less prevalent in the pediatric population 
    • In the United States, 22% of the population is made up of children <18 years 
    • However,  they represented only an estimated 1.7% of total COVID-19 cases
  • The median age of pediatric patients was determined to be 11 years
    • Infants (i.e. babies <1 year) are 15% of these patients 
  • Like adults, the three most common symptoms in patients ages 0-18 are fever, cough, and shortness of breath
    • 73% of patients presented with at least one of these three symptoms
    • This is less common than adults (93% present with at least one)
  • An estimated 23% of pediatric cases have at least one underlying condition 
    • The three most prevalent are chronic lung disease (including asthma), cardiovascular disease, and immunosuppression 
    • These cases tended to be more severe (i.e.hospital admission), though death is rare

Study Title: The Epidemiological Characteristics of an outbreak of 2019 novel coronavirus disease (COVID-19) in China. 

https://www.ncbi.nlm.nih.gov/pubmed/32064853

Brief Summary: Researchers in China accessed over 70,000 patient records to calculate key data on the COVID-19 epidemic. They calculated that 81% of cases were considered to be clinically “mild” and that a total of 1,023 deaths had occured at the time of analysis, giving an overall case fatality rate of 2.3% 

Background

  • This study aimed to describe demographics and clinical data in patients with confirmed or suspected COVID-19 

Methods 

  • Data on all COVID-19 cases reported to China’s Infectious Disease Information System through February 11, 2020 were examined 
  • A total of 72,314 patient records were included, which consisted of 
    • 44,672 (61.8%) confirmed cases 
    • 16,186 (22.4%) suspected cases 
    • 10,567 (14.6%) clinically diagnosed cases 
    • 880 (1.2%) asymptomatic cases 

Results: Authors determined the following descriptive characteristics among laboratory-confirmed cases

  • 86.6% were in persons aged 30-79 years 
  • The severity of cases is as follows: 
    • 80.9% of cases were considered to be “mild” 
    • 14% of patients displayed severe symptoms (i.e. dyspnea, hypoxia)
    • 5% of patients displayed critical symptoms (i.e. respiratory failure, shock)
  • A total of 1,023 deaths occurred, leading to an overall case-fatality rate of 2.3% 
  • 1716 health workers had become infected, with 5 (0.3%) dying 

Conclusions: The COVID-19 epidemic in China originated in the Hubei province and quickly spread to the rest of mainland China. Thus, China needs to enact precautions to prevent a rebound epidemic. Data shows the majority of cases are “mild” with the majority of people recovering. 

Study Title: Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) — United States, February 12–March 16, 2020

https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm

Brief Summary: The CDC looked at preliminary data on 4,226 COVID-19 reported CDC cases. They estimated that 80% of deaths were in patients ages 65 and older and that members of this age group were more likely to have serious disease. Thus, the CDC advises special precautions in this age group such as avoiding large crowds. 

Background

  • Early data from China suggests that a majority of COVID-19 deaths have occurred among elderly population aged 60 or older and/or person with underlying health conditions 

Methods 

  • The CDC analyzed cases of laboratory confirmed COVID-19 reported from February 12-March 16 
  • Cases were reported from 49 states, the District of Columbia, and 3 U.S. territories 
  • Data on these cases were based off of preliminary data and some important characteristics of interest (i.e. death) were missing
    • Hence, the authors reported data as an estimated range 

Results 

  • As of March 16, a total of 4,226 COVID-19 cases had been reported to the CDC 
  • Overall, 31% of cases, 45% of hospitalization, 53% of ICU admissions, and 80% of deaths were among adults ages 65 of older 
  • CDC provided percentage range estimates on hospitalization, ICU admission, and death by age group; older age was associated with higher rate of death 

Conclusion: Based on early data of the COVID-19 pandemic in the US, serious adverse outcomes including death are higher in persons 65 and older. Social distancing is recommended for people to all ages in order to stop the transmission of the virus especially to older adults. Additionally, older adults should take special precautions, including maintaining a large supply of nonperishable foods and avoiding crowds as much as possible. 

Study Title: Baseline Characteristics and Outcomes of 1591 Patients Infected with SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy 

https://jamanetwork.com/journals/jama/fullarticle/2764365

Brief Summary: This study examined 1591 patients admitted to the intensive care units (ICU) of hospitals in the region of Lombardy, Italy. Researchers determined that the median age of admitted patients was 63 years, 1304 (82%) were male, and 709 (68%) had at least one underlying health condition. The mortality rate of patients admitted to the ICU was estimated to be 26%.

Background 

  • The authors aimed to describe patients with COVID-19 requiring treatment in the ICU in the Italian region of Lombardy 

Methods 

  • Authors conducted a retrospective case series of 1591 patients that tested positive for COVID-19 via RT-PCR assay of nasal and pharyngeal swabs 
  • These patients were admitted to one of the ICU units of the 72 hospitals in the Lombardy region of Italy 
  • Admission occurred February 20 and March 18, 2020, with final follow-up on March 25, 2020

Results

  • Patient demographics and clinical data were collected, including mortality, management, and respiratory failure 
  • The median age of the patients was 63 years and 1304 (82%) were male 
  • Of the 1043 patients with prior data, 709 (68%) had at least one comorbidity with the most common being hypertension 509 (49%) 
  • Of the 1300 patients with respiratory data
    • 1287 (99%) needed respiratory support 
    • 1150 (88%) needed mechanical ventilation 
    • 137 (11%) received noninvasive ventilation 
  • Of the 1581 patients with ICU disposition data 
    • 920 (58%) were in the ICU 
    • 256 (16%) were discharged 
    • 405 (26%) had died in the ICU 
  • The 786 patients age 64 or greater had a higher mortality rate (36%) compared to the 795 patients age 63 and younger (15%) 
    • Difference of 21% 

Conclusion: In this study of critically ill COVID-19 patients admitted to ICUs in Lombardy, Italy, the majority were male, older, and had an underlying health condition (i.e. hypertension). A large proportion required mechanical ventilation. ICU mortality, calculated 7 days after the final set of patients in the study were admitted, was 26% and was higher in patients aged 64 and greater. 

Study Title: A systematic Review of COVID-19 Based on Current Evidence 

https://www.mdpi.com/2077-0383/9/4/967/htm

Brief Summary: This review aims to generate epidemiological data on COVID-19 based on 41 studies. Key estimates include an incubation period of 4-6 days and a case fatality rate of 0.3-1.4% outside of China. While more research is needed, these data can guide public health and clinical efforts in containing the transmission of the virus. 

Background

  • The authors aimed to identify and summarize evidence on the epidemiological characteristics of SARS-CoV-2 

Methods 

  • The authors generated 317 research articles from an initial search on PubMed
  • A total of 41 met the inclusion criteria and included in the review 
  • These studies were published up to mid-February, and thus do not include some of the newest literature 

Results 

  • Evidence suggests it takes 3-7 days for the epidemic to double in size 
  • Reproduction number is estimated to range from 1.9 to 6.5, with 13 studies estimating 2-3 
    • Defined as the “average number of secondary cases generated by an index case in a susceptible population”
  • Incubation period: Estimated to be 4-6 days 
    • Defined as time from exposure to onset of symptoms 
  • Serial Interval: Estimated to be 4-8 days 
    • Defined as time from symptom onset of a primary case to a secondary case
  • Case Fatality rate: Ranged from 0.3% to 1.4% outside of China
    • Defined as number of deaths in patients that have COVID-19 over total number of cases
    • Authors emphasize this is preliminary as we have not reached the peak of the COVID-19 pandemic and data is evolving 

Conclusion: This study uses existing literature to generate key figures related to the COVID-19 pandemic. These can be used to inform policy at the hospital, institutional, and government levels. As the COVID-19 pandemic continues to proliferate through the world, there is a critical need for continued high-quality research on the topic.

Study Title: Epidemiology of Covid-19 in a Long-term Care Facility in King County, Washington 

https://www.nejm.org/doi/full/10.1056/NEJMoa2005412

Brief Summary: Long-term care facilities, such as nursing homes, have residents and staff that are particularly vulnerable to infection by Covid-19. In February of this year, a case of Covid-19 was confirmed in an elderly patient in a nursing facility near Seattle, Washington. Eventually, a total of 101 cases of Covid-19 among residents were identified with a fatality rate of 33.7% (34/101). An additional 50 staff and 16 visitors were also infected. This initial cluster emphasizes the importance of early identification of residents and staff infected in Covid-19 in terms of preventing further spread and adverse outcomes including death.   

Background 

  • Long-term care facilities are high-risk settings for outbreaks of Covid-19 due to the elderly age and multiple chronic health conditions of the residents 
  • Transmission is further facilitated due to close contact between residents and health care personnel. 

Methods

  • On February 28, 2020, a case of Covid-19 was confirmed in a 73 year-old patient living in a skilled nursing facility in King County, Washington who was admitted to a local hospital
  • In response, Public Health-Seattle and King County (PHSKC) and the Centers for Disease Control and Prevention immediately coordinated a joint investigation into the transmission and infection control of Covid-19. 

Results

  • As of March 18, there were a total of 167 confirmed cases of Covid-19
  • An estimated 101 residents, 50 healthcare personnel, and 16 visitors were linked to the facility
  • The majority of facility residents experienced respiratory illness consistent with Covid-19; however, 7 were asymptomatic 
  • Hospitalization rates for facility residents was 54.5%, 50.0% for visitors, and 6.0% for staff.
  • The case fatality rate for the residents was 33.7% (34/101)
  • The vast majority of these patients (94.1%) had at least one underlying chronic health condition, with the most common being hypertension
  • Factors that promoted Covid-19 transmission among healthcare personnel included working while symptomatic and insufficient personal protective equipment
  • As of March 18, a total of 30 long-term care facilities in King County had at least one confirmed case of Covid-19.

Conclusion 

  • Once Covid-19 infection is introduced to a long-term care facility, it has the ability to spread quickly among residents, staff, and visitors and lead to adverse outcomes including death
  • This emphasizes the importance of recognizing possible infected patients early, identifying and excluding staff and visitors that may have been infected, and prevention measures. Lessons from this initial cluster can be used to guide other prevention and management of Covid-19 in other long-term care facilities in The United States. 

Study Title: The effect of control strategies to reduce social mixing on outcomes of the COVID-19 epidemic in Wuhan, China: a modelling study

https://www.thelancet.com/action/showPdf?pii=S2468-2667%2820%2930073-6

Brief Summary: Physical distancing measures, such as school and work closures, have been effective in reducing the spread of COVID-19 in Wuhan, China. Projections indicate that these measures should be maintained until at least mid-April to prevent overwhelming the Chinese healthcare system. These findings can be applied to other countries such as The US.

Background 

  • In December of 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), often referred to as COVID019, emerged in Wuhan, China
  • Since then, the city has taken drastic efforts to reduce the spread of the virus
  • This paper examined the impact of these efforts in reducing transmission 

Methods of Study 

  • To examine the effects of these measures, the authors created mathematical models that simulate the reduction in human to human contact done by extended workplace closures, school closures, and general social distancing policies 
  • The authors also simulated what would happen to the spread of COVID-19 by examining the effects of lifting extended work closure in early March or April

Results

  • The projects showed that physical distancing measured were most effective if resuming work occured at the beginning of April; 
    • Specifically, this reduced the median amount of infections by more than 92% by mid-2020 and 24% by end of 2020 
  • Further benefits included delaying and decreasing the peak of COVID-19 cases and allowing the healthcare system more time to respond and improve infractures 
  • The authors proposed limitations of their measurements included uncertainty about the duration of infectiousness of COVID-19 and the role children play in the epidemic 

Interpretation 

  • Physical distancing measures in Wuhan China, if maintained until April, will help to significantly reduce the total number and peak number of COVID-19 cases. 
  • Lifting these interventions prematurely and suddenly could lead an increase in total and peak COVID-19 cases. 
  • This can be applied to other countries such as the US as reason to continue strict physical distancing measures. 

Study Title: Temperature, Humidity, and Latitude Analysis to Estimate Potential Spread and Seasonality of Coronavirus Disease 2019 (COVID-19)

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2767010?resultClick=1

Brief Summary: Research suggests COVID-19 transmission follows seasonal patterns similar to other human coronaviruses and respiratory viruses. This study analyzed climate patterns between Jan to March 10th 2020 from 50 cities either heavily, lightly, or not affected by COVID-19. The researchers found restricted parameters of latitude, temperature and humidity associated with areas substantially affected by COVID-19, thereby suggesting climate can be used to predict future transmission patterns that can inform timely implementation of appropriate disease control and surveillance measures.  

Background: Given the rapid spread of the COVID-19 pandemic and the way in which it overwhelmed public health infrastructure globally, many are concerned about the unpredictability over the virus’ future patterns of attack and over the uncertainty for which populations and areas are most at-risk. Previous epidemiological research has revealed the important roles of ambient temperature, humidity and seasonality in survival and transmission of various respiratory viruses, including influenza and human coronaviruses. Thus, the purpose of this cohort study was to determine if climate could be used as a significant factor to predict future transmission of COVID-19 using lab data and mathematical modeling.  

Methods: Comparisons of climate data reported between Jan 1st to March 10th 2020 from 8 cities

heavily affected by COVID-19 (Wuhan, China; Tokyo, Japan; Daegu, South Korea; Qom, Iran; Milan, Italy; Paris, France; Seattle US; Madrid, Spain) to 42 cities either affected to a lesser degree or not affected.    

Key Results:

  • Similar climate trends exhibited in the 8 heavily affected cities: 
    • Average temperatures of 5 to 11°C 
    • Low specific and absolute humidity 
    • Substantial community COVID-19 transmission heavily distributed along the 30°N to 50°N latitude corridor   

Conclusion: Based on the data, the researchers identified specific parameters of latitude, temperature and humidity that are consistent with patterns of COVID-19 transmission and outbreak behavior. These climate parameters behave seasonally, which further suggests that COVID-19 acts similar to other seasonal respiratory viruses. This finding creates a potential opportunity for development of surveillance strategies to anticipate future transmission patterns and promote early identification of at-risk areas and populations for outbreak control and disease prevention.   

Study Title: COVID-19 Pandemic: Exacerbating Racial/Ethnic Disparities in Long-Term Services and Support 

https://doi.org/10.1080/08959420.2020.1772004

Brief Summary: This literature review examines how pre-existing racial and ethnic disparities and inequities in long-term services and support (LTSS) facilities have worsened within context of the COVID-19 pandemic. 

Background: LTSS facilities, such as nursing homes and assisted living, are traditionally associated with health care racial and ethnic disparities against colored and indigenous individuals. Such health disparities encompass but are not limited to lack of health insurance, inadequate access to quality care, cumulative social determinants of health related adversity, and inequities within the health care workforce. Given the baseline, these disparities have only become exacerbated due to the COVID-19 pandemic, and has consequently been attributed to increased risk of COVID-19 infection and premature mortality among ethnic/racial minority individuals using LTSS facilities as compared to their Caucasian peers. 

Key Findings based on previous research:

  • A larger concentration of racial and ethnic minorities (African Americans and Hispanics) receive care in lower performing clinical settings, many of which are located in overcrowded urban communities associated with increased count of COVID-19 cases and risk of COVID-19 infection.
  • LTSS facilities with a majority proportion of minority residents report lower average quality of life partly due to limited resources and personnel as compared to other facilities with a majority proportion of Caucasian residents.
  • Lack of state support for LTSS facilities means they rely on expensive private laboratories to receive COVID-19 testing, thus making it difficult for minorities who are more likely to struggle financially to afford the test.  
  • Language barriers due to poor translation services in health care LTSS facilities is associated with poor quality of care and patient social isolation, which is exacerbated with COVID-19 social distancing measures.
  • African American healthcare staff have more work strain and burnout compared to their Caucasian counterparts.
  • Ethnic minorities within the health care workforce are more likely to work in urban areas and use public transport to get to work, increasing their risk of COVID-19 infection and risk of spreading it to their patients. 

Conclusion: The healthcare system is intrinsically ridden with inequities that has caused minority populations to have worse health outcomes for far too long. In light of the COVID-19 pandemic exacerbating and highlighting these disparities, action needs to be taken in the form of physician advocacy and health policy reform. Recommendations include improving pay and LTSS work conditions, holding LTSS facilities accountable by including quality of care as an assessment metric, prioritizing COVID-19 testing and PPE resources to LTSS facilities with a high proportion of minority residents, and reporting COVID-19 cases in LTSS facilities by race/ethnicity for further research. 

Metabolic Dysfunction Associated Fatty Liver Disease Increases Risk of Severe COVID-19 

Link:https://reader.elsevier.com/reader/sd/pii/S187140212030182X?token=452B280D32DC16891C6EC59F4BA6A1F264A4B178DF393347A9AF9C94CA830BE5A31E60F4CBDD43B19D5D4D625AFD1044

Brief Summary: Metabolic dysfunction associated fatty liver disease is an increasing public health burden as obesity rates continue to skyrocket around the world, notably in developed countries. Based on known COVID-19 lab findings suggesting dysregulated liver function and previous research associating metabolic syndrome as a risk factor for severe COVID-19 infection, the researchers aimed to conduct a systematic review studying the outcomes of COVID-19 infected MAFLD patients. They suggest COVID-19 infected MAFLD patients have a 4-6 times increased risk of severe COVID-19 infection, which is further associated with older age and liver fibrosis due to MAFLD pathophysiology.      

Background: Typical clinical lab findings in COVID-19 patients include elevated liver enzymes called ALT and AST, elevation of a blood enzyme called alkaline phosphatase (ALP), and slight serum elevation of the heme breakdown product called bilirubin. All these lab measures are indicative of deranged liver function, which if persistent overtime can increase risk for liver failure, hemodynamic instability and other fatal consequences. Based on these observations, the researchers conducted a systematic review to analyze the risks and outcomes of COVID-19 infection in patients co-diagnosed with comorbid conditions like fatty liver, metabolic dysfunction associated fatty liver disease (MAFLD), and non-alcoholic fatty liver disease (NAFLD) that are independently known to cause abnormal liver function as compared to COVID-19 patients lacking these comorbid conditions.     

Methods: The PubMed database was systematically searched until May 20th, 2020 for all studies published on exploring the relationship between COVID-19 infection and fatty liver/MAFLD/NAFLD. The researchers note that this area of study is very limited in scope.

Key Results: 

  • 4 to 6 times increased risk of developing severe COVID-19 infection in patients co-diagnosed with MAFLD.
  • 60 year-old patients with severe liver fibrosis, MAFLD, and obesity were associated with increased risk for developing severe COVID-19 infection. 
  • COVID-19 infected MAFLD patients are significantly associated with an increased viral shedding duration as compared to COVID-19 patients without MAFLD.  

Conclusion: Despite the limited scope of data, studies suggest that COVID-19 infection in patients with MAFLD is more severe than in patients without MAFLD. Researchers hypothesize that this increased severity may be linked to the primed robust pro-inflammatory immune response in MAFLD patients created due to underlying liver fibrosis that serves to exacerbate the pro-inflammatory mechanisms of the COVID-19 virus. Exacerbation of the pro-inflammatory response overwhelms the immune system, resulting in further liver function derangement and homeostatic instability. Further research is needed to confirm this hypothesized pathophysiology. 

Hospitalization and Mortality among Black Patients and White Patients with Covid-19

Link: https://www.nejm.org/doi/pdf/10.1056/NEJMsa2011686?articleTools=true

Brief Summary: The purpose of this retrospective cohort study was to identify and characterize differences in health outcomes, including hospitalization and in-hospital mortality outcomes, among 3,481 black and white patients infected with Covid-19 at an integrated-delivery health system in Louisiana. The researchers reported black patients exhibit higher rates of socioeconomic disparities and co-morbid conditions known to exacerbate Covid-19 infection. However, results indicate little disparities in terms of quality of care based on race.   

Background: Current epidemiological studies on Covid-19 have characterized the viral illness as affecting individuals of all sexes, ages and health statuses, with those 65 and older and those with chronic cardiovascular, pulmonary, and metabolic co-morbidities classified as most high-risk. However, data about racial- and ethnic- specific differences in health outcomes due to Covid-19 is lacking and requires research. Thus, the purpose of this retrospective cohort study was to identify and characterize differences in health outcomes, including hospitalization and in-hospital mortality outcomes, among black and white patients infected with Covid-19 at a healthcare system in Louisiana.   

Methods: The cohort population consisted of 3,481 Covid-19 positive patients seen within an integrated-delivery health system in Louisiana between March 1stand April 11th2020, among whom 60% were female, 70.4% were black non-Hispanic, and 29.6% were white non-Hispanic. All patients tested positive for Covid-19 via qualitative PCR assay. Hospitalization and in-hospital mortality outcomes were assessed between white and black patients. 

Results:

  • The % of black patients with Medicaid insurance was 3X as high as the % of white patients
  • Black patients were 2X more likely to live in low-income areas as compared to white patients 
  • Black patients had a higher prevalence of obesity, diabetes, hypertension, and chronic kidney disease than white patients 
  • Average length of hospital stay was similar for black and white patients

Conclusion:  Within an integrated-delivery health system in Louisiana with a 31% black patient population, an overwhelming majority of patients hospitalized with Covid-19 (76.9%) and those who passed (70.6%) from the viral illness are/were black. Moreover, statistical analysis suggests black and white patients experience similar in-hospital mortality outcomes even when adjusted for sociodemographic and clinical factors. Based on this data, it is evident that racially-driven health disparities within certain but not all areas of the healthcare system exist, and more research needs to be done to further evaluate and resolve such differences in health outcomes.

What settings have been linked to SARS-CoV-2 transmission clusters?

Link: https://wellcomeopenresearch.org/articles/5-83/v2  

Brief Summary: This systematic review analyzes scientific literature and media reports on mass COVID-19 transmission events to try and identify indoor/outdoor public settings that are high risk infection transmission clusters. The researchers identified several indoor public locations that serve as transmission clusters, suggesting these locations should be placed under strict surveillance or opening restrictions as countries and states implement their phased re-opening strategies.    

Background: With many countries implementing phased re-openings, there is a need to concretely identify indoor and outdoor public settings where there is high risk for COVID-19 transmission in order to inform re-opening strategies and beneficially shape global public health policy. Thus, the purpose of this systematic review was to identify so called transmission clusters with the goal of ensuring such public settings remain under strict surveillance or closed as countries and states execute their phased reopening strategies. 

Methods: The researchers searched scientific literature (62 articles total) via PubMed and several national media reports via Google search engine to find public settings and events around the world that were reported on as being clusters for COVID-19 transmission based on the number of cases associated with such locations. 22 indoor/outdoor settings were identified from the 201 events in which COVID-19 transmission occurred.

Results: Majority of COVID-19 transmission clusters were public indoor settings. 

Conclusion: Based on reported COVID-19 transmission cluster events, the researchers highlighted public settings that pose variable risk for spread of infection. Notably, the data suggests countries may want to impose stricter surveillance or opening restrictions on bars, elderly care facilities, food processing plants, hospitals, households, prisons, religious venues, schools, ships, shopping centers, weddings, sporting events and worker dormitories. While more research needs to be conducted to identify transmission cluster hotspots, this research provides preliminary data that can influence the design of country or state phased re-opening strategies.   

As of 10/19/20

Date: 10/14/2020

Study title:Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates

Link:https://www.nejm.org/doi/full/10.1056/NEJMoa2027906?query=featured_coronavirus 

Summary: This randomized controlled trial published by NEJM assess the safety and immunogenicity of two SARS-CoV-2 RNA candidate vaccines: BNT162b1 and BNT162b2. The researchers found that the BNT162b2 is safer and that both candidate vaccines present with a similar immunogenicity profile. Based on these findings, the BNT162b2 vaccine will be advanced to a pivotal phase 2-3 safety and efficacy evaluation. 

Background: The purpose of this randomized controlled trial was to assess the safety and immunogenicity of the BNT162b1 and BNT162b2 SARS-CoV-2 RNA candidate vaccines in healthy adults aged 18 to 55 and 65 to 85 years old.   

Methods: This is an ongoing placebo-controlled and double blinded phase 1 clinical trial being conducted in the United States. Vaccinated subjects are being assessed for two outcomes: safety and immunogenicity. Safety includes screening for vaccine-induced local and systemic side effects and adverse outcomes. Immunogenicity is the ability for an antigen to elicit an immune response that helps the body fight off infection. In short, immunogenicity assesses whether the vaccine is significantly effective in preventing COVID-19 infection. In total, 195 participants were randomized to either receive the placebo, the BNT162b1 vaccine, or the BNT162b2 vaccine. Moreover, participants receiving a COVID-19 candidate vaccine were injected with either a 10 μg, 20 μg, 30 μg, or 100 μg dosage. Also, most participants received two injections of their assigned dose with a 21-day interval between doses, except for those who received a 100 μg dose.   

Results: The researchers have thus far concluded that the BNT162b2 candidate vaccine is safer due to showing a reduced risk of local and systemic side effects as compared to the BNT162b1 candidate vaccine, especially in those aged 65 to 85 years old. Both candidate vaccines exhibited similar dose-dependent immunogenicity in both the younger and older cohorts of adults. Specifically, IgG antibody response and virus neutralizing response was most maximal for participants administered the 10 μg to 30 μg doses. Also, immunogenicity was generally lower in the 65 to 85 year-old cohort than in the 18 to 55 year-old cohort. which is justified by the fact that aging dampens the body’s ability to generate an immune response. The researchers are still determining whether this data is statistically significant. 

Conclusion: Based on the results, the researchers have enough evidence to advance the BNT162b2 candidate vaccine to a pivotal phase 2-3 safety and efficacy evaluation.  

Study title: Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2:A preliminary report of a phase 1/2, single-blind, randomized controlled trial

Link: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31604-4/fulltext

Publication date: 07/20/20

Background: This phase 1/2, single-blind, randomized control trial tested the safety, side effects, and immunogenicity of a viral vectored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine that expresses the spike protein of SARS-CoV-2 called ChAdOx1 nCoV-19. Results were compared to the same parameters of the meningococcal conjugate vaccine called MenACWY, which served as the standard/control.

  • A phase ½ randomized control trial is a study that tests:

o   How well a disease responds to a new treatment compared to an accepted standard/control

o   The safety of the new treatment

o   Side effects of the new treatment

o  Optimal dosage of a new treatment 

  • Single-blinded means that only the researcher(s) conducting the study know whether participants are receiving the experimental intervention (i.e. SARS-CoV-2 vaccine) or standard/control (meningococcal conjugate vaccine). The participants do not know which vaccine they received until after the trial is over.    
  • A viral vectored vaccine uses live viruses to carry viral DNA that encodes antigens into human cells. Antigens are foreign substances that elicit an immune response in the body. Thus, when viral DNA enters an infected human cell and expresses its antigens, the body will elicit an immune response to fight off the viral infection.  
  • Immunogenicity is the ability for an antigen to elicit an immune response that helps the body fight off infection. 
  • The SARS-CoV-2 spike protein helps the SARS-CoV-2 enter into human cells, hence the purpose of using it to design a viral vectored vaccine. 

Methods: 

  • The trials were conducted at 5 sites in the UK on 1,077 participants, 543 who received the experimental ChAdOx1 nCoV-19 vaccine and 534 who received the control MenACWY vaccine.    
  • Outcomes assessed included:

o   Baseline and post-vaccination humoral immune responses using immunoassays

o   Vaccine efficacy, measured by number of symptomatic and lab confirmed SARS-CoV-2 cases

o   Vaccine safety, measured by number of vaccine-induced serious adverse events, was assessed 28-days post vaccination  

Results: 

  • Minor vaccine-induced adverse reactions (i.e. pain, feverish, chills, muscle aches, headaches, fatigue) were more frequent in the ChAdOx1 nCoV-19 vaccine group, and such reactions could mostly be controlled via prophylactic medications.  
  • There were no recorded serious adverse events elicited by the ChAdOx1 nCoV-19 vaccine.   
  • The ChAdOx1 nCoV-19 induced a promisingly robust humoral immune response, especially after administration of a booster dose.  

Conclusion: The ChAdOx1 nCoV-19 shows acceptable vaccine safety, as well as promising vaccine efficacy as presented by the vaccine’s ability to induce a robust humoral and cellular immune responses and likely limit COVID infection. These results support the need for progression of the ongoing ChAdOx1 nCoV-19 vaccine trials onto further phases.   

An mRNA Vaccine against SARS-CoV-2 — Preliminary Report

Link: https://www.nejm.org/doi/full/10.1056/NEJMoa2022483 

Publication date: 07/14/20

Background: 

  • Phase 1 clinical trial to evaluate the safety and efficacy of this vaccine 
  • What is a phase 1 clinical trial?
    • Testing of the drug on healthy volunteers for safety; involves testing multiple doses 
    • Goal: Determines whether the drug is safe to check for efficacy 
  • What is a messenger RNA (mRNA)?
    • mRNA definition: inside the human body, messenger RNA supplies the information that DNA uses to make proteins, which regulates our cells and tissues. 
    • Viruses use RNA for a more damaging purpose
    • Viruses invade healthy cells and multiply within health cells, sometimes causing sickness or death 
    • Ex. The mRNA in COVID-19 enables a “spike protein” that pierces cells throughout the body. This is particularly damaging whenever the virus invades the lungs, making the simple act of breathing challenging 
  • What is a mRNA vaccine? 
    • An mRNA vaccine contains a synthetic (made in a laboratory) version of RNA that a virus uses to form proteins 
    • The vaccine does not contain enough genetic information to produce viral proteins; just enough to prime the immune system into thinking a virus is present so that it will spring into action to make antibodies.
    • Antibodies are proteins specifically designed to fight a virus
    • Making antibodies prior to actually being infected allows the body to have enough immunity to essentially block the virus from damaging the body

Methods: 

  • 45 healthy adults, ages 18-55 years of age 
  • Each participant received 2 vaccinations, 28 days apart 
  • Three different dosages were tested
  • 15 participants in each dose group 

Results: 

  • After the first vaccination, antibody responses were higher with a higher dose 
  • After the second vaccination, the antibody levels were higher and detected in all participants
  • Adverse events that occurred in more than half of the participants included: 
    • Fatigue
    • Chills
    • Headache 
    • Myalgia 
    • Pain at injection site 
  • Systemic adverse events were more common after the second vaccination, particularly with the highest dose. 
  • Three participants (21%) in the highest dose group on the second vaccination reported one or more severe adverse events

Conclusion: These safety and efficacy findings support advancement of this particular mRNA vaccine to later-stage clinical trials.  

A brief 1-3 sentence summary is included at the top of each article followed by a more in depth analysis of the article. The articles are divided into three sections: Management, Epidemiology & Transmission, and Foundational Articles.

Management 

Date: 09/08/2020

Study title: Evaluation of the Risk Prediction Tools for Patients with Coronavirus Disease 2019 in Wuhan, China

Link: https://www.ncbi.nlm.nih.gov/research/coronavirus/publication/32897668

Summary: This study identified the National Early Warning score and oxygen saturation score as efficacious risk stratification tools for predicting in-hospital mortality due to COVID-19. 

Background:The purpose of this retrospective observational study was to identify which pre-existing risk stratification tool is most efficacious for predicting in-hospital death in COVID-19 patients. The following widely accepted risk stratification tools which were assessed included: the National Early Warning Score, the National Early Warning Score 2, the Rapid Emergency Medicine Score, confusion, respiratory rate, blood pressure, the Age 65 score, and the Sepsis-Related Organ Failure Assessment. By identifying the risk stratification tool most efficacious at predicting degree of illness, the researchers aimed to target these patient for immediate critical care intervention with the goal of reducing in-hospital death due to COVID-19.   

Methods: 673 adult COVID-19 patients (51% male, between 50-69 years) between January 30thand March 14th2020 seeking treatment at West Campus of Wuhan Union hospital in Wuhan, China were included in the study. Date about demographics, pre-existing comorbidities, vitals, mental status, oxygen saturation, and supplemental oxygen upon admission were extracted from medical records and used to score all the aforementioned risk stratification tools for each patient to predict their risk of in-hospital mortality. Mortality outcomes were compared to the predicted scores. It was reported that 121 patients (18% of the sample) died due to COVID-19.

Table 1: Characteristics of the study cohort.

Results:

What is an ROC curve? ROC curvesare a graphical depiction illustrating the connection/trade-off between clinical sensitivity and specificity for every possible cut-off for a test or a combination of tests.

What is the main finding of the study’s ROC curve? This study’s ROC curve compares the specificity and sensitivity of the various risk stratification tools for predicting in-hospital death due to COVID-19. The main finding is: the National Early Warning/ National Early Warning 2 Score and the oxygen saturation score were the most significant predictors of in-hospital death. 

Conclusion: Based on the results, the researchers suggest the efficacy of the National Early Warning/ National Early Warning 2 Score and oxygen saturation score are most accurate in predicting in-hospital death due to COVID-19. This finding is important because it can help healthcare providers identify patients with poor prognosis who are in need of critical care intervention, with the ultimate goal of reducing in-hospital mortality due to COVID-19. More research needs to be conducted to replicate and confirm these results.    

Date: 09/07/2020

Study Title: Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients with COVID-19 

Link: https://jamanetwork.com/journals/jama/fullarticle/2770279

Brief Summary: This prospective meta-analysis looked at 7 randomized controlled trials with a total of 1703 patients to determine if systemic corticosteroids reduce 28-day mortality. The authors determined that 28-day mortality was lower in critically ill COVID-19 positive patients who received corticosteroids compared with standard care (odds ratio of 0.66). 

Background: Corticosteroids, such as low-dose dexamethasone, have shown promise in reducing mortality in certain cases in COVID-19 patients who are hospitalized. The authors of this study conducted a meta-analysis on existing studies that examined the role of low-dose dexamethasone in managing patients with COVID-19. 

Methods: The authors conducted a prospective meta-analysis that included data from 7 randomized clinical trials conducted in 12 countries between February 26, 2020 to June 9, 2020. In total, these studies included 1703 critically ill patients with COVID-19; the median age of these patients was 60 years and 29% were women. In total, 678 patients received one of the systemic corticosteroids of dexamethasone, hydrocortisone, or methylprednisolone and the other 1025 served as placebo. The main outcomes measured were all-cause mortality (i.e. death for any reason) 28 days after randomization and serious adverse effects. 

Results

The primary results were as follows:

  • There were 222 deaths among the 678 patients who received one of the three corticosteroids 
  • There were 425 deaths among the 1025 patients who received usual care 
  • The odd ratio of death was 0.66 (P<0.001), which is statistically significant; this suggests that corticosteroids carry a mortality benefit 
  • This relationship was strongest for Dexamethasone, which had a mortality odds ratio of 0.64 (P< .001)
  • In contrast, hydrocortisone and methylprednisolone did not has a statistically significant mortality benefit 

The secondary results were as follows: 

  • Risk of bias was characterized as “low” for 6 out of the 7 studies, suggesting high quality of data 
  • Six trials reported serious adverse effects
    • 64 events occurred in the 354 patients that received corticosteroids
    • 80 events occurs in the 342 patients randomized to usual care or placebo

Conclusions: Administration of systemic corticosteroids, particularly low-dose dexamethasone, is associated with a lower mortality rate at 28 days. 

Date: 8/6/20

Link: https://www.nejm.org/doi/full/10.1056/NEJMoa2016638?query=recirc_mostViewed_railB_article

Study Title: A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19

Background: 

  • Randomized, double blind, placebo controlled trial across the US and parts of Canada
  • Tested hydroxychloroquine as postexposure prophylaxis 

Methods: 

  • Subjects were adults with a confirmed COVID-19 household or occupational exposure at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high risk exposure) or while wearing a face mask but no eye shield (moderate risk exposure) 
  • Within 4 days of exposure participants were randomly assigned to either placebo or hydroxychloroquine 
  • Primary outcome was the incidence of either laboratory confirmed COVID-19 or illness compatible with COVID-19 within 14 days of exposure 

Results: 

  • n=821 asymptomatic participants 
  • 87.6% had a high risk exposure 
  • The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]); the absolute difference was −2.4 percentage points (95% confidence interval, −7.0 to 2.2; P=0.35). 
  • Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported.

Conclusions: 

  • After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure. 

Date: 07/31/2020

Study title: Acetylated K676 TGFBIp as a severity diagnostic blood biomarker for SARS-CoV-2 pneumonia

Link: https://advances.sciencemag.org/content/advances/6/31/eabc1564.full.pdf

Summary: This study found that TGFβIp and TGFBIp K676Ac, immune system signaling molecules, can potentially be used as blood biomarkers for differentiating critically ill COVID-19 cases at risk for pneumonia and in need of urgent ICU care from less symptomatic COVID-19 patients.      

Background: The death toll due to COVID-19 is continuously rising daily, thus creating an urgent need for tools that can be used to target severely ill patients requiring immediate intervention. This study identified transforming growth factor-beta (TGFβ), a cytokine/cell-signaling molecule, as a reliable blood biomarker that can potentially be used as prognostic and therapeutic tool for distinguishing severely symptomatic COVID-19 patients.     

Methods: Levels of TGFβIp (a TGFβ-induced protein) and TGFBIp K676Ac (a post-translationally modified TGFβ-induced protein) in the blood were measured using an ELISA assay in 113 COVID-19 positive patients residing in either an ICU (10 patients) or non ICU (85 patients) settings. Plasma was collected from 20 healthy non-COVID positive individuals and analyzed as a control. 

Results: Scatterplots A and B compare levels of TGFβIp and TGFBIp K676Ac, respectively, among healthy individuals, COVID-19 non-ICU cases, COVID-19 ICU cases, and recovered and discharged COVID-19 cases. Both measured serum biomarkers were significantly elevated in severely ill ICU cases as compared to mildly ill non-ICU cases, recovered/discharged cases, and non-COVID patients. Also, both biomarkers were also significantly increased in non-ICU cases as compared to recovered/discharged and non-COVID patients.   

Conclusion: The data suggests serum TGFβIp and TGFBIp K676Ac levels are blood biomarkers that can be used as a predictive prognostic and therapeutic decision making tools for targeting critically ill COVID-19 patients in order to provide optimal life-saving care. Implications of this research include potential to reduce in-hospital mortality due to COVID-19.     

Date: 07/20/20

Study Title: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial

Link: https://www.sciencedirect.com/science/article/pii/S0924857920300996

Background: The authors evaluate the effectiveness of hydroxychloroquine on respiratory viral loads. 

Methods: 

  • Location France
  • n=42; hydroxychloroquine n=26 and control n=16
  • Treatment: 600 mg of hydroxychloroquine daily (azithromycin was added based on clinical presentation)  
  • Measurement: viral load of nasopharyngeal swabs 
  • Comparison: untreated patients from another center or cases refusing the protocol) 
  • End point: presence or absence of virus at Day 6 

Results: 

  • Figure taken from paper. Percentage of patients with PCR positive nasopharyngeal samples from inclusion to day 6. 
  • Note post day 3 from study start those on hydroxychloroquine and those on hydroxychloroquine and azithromycin had significantly lower positive COVID-19 tests when compared to control.

Conclusions:

  • Hydroxychloroquine is efficient in clearing viral nasopharyngeal carriage of SARS-CoV-2 in COVID-19 patients in only three to six days, in most patients.
  • The results suggest a synergistic effect of the combination of hydroxychloroquine and azithromycin. Azithromycin has been shown to be active in vitro against Zika and Ebola viruses 
  • In some cases hydroxychloroquine failed. The cause for a failure of hydroxychloroquine treatment should be investigated by testing the isolated SARS-CoV-2 strains of the non-respondents and analyzing their genome, and by analyzing the host factors that may be associated with the metabolism of hydroxychloroquine.

Study Title: Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019

Original Article: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2767593

JAMA Commentary: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2767588

Brief Summary: In this study from Greece, authors evaluated the clinical and biochemical effects of the gout drug colchicine in patients hospitalized for COVID-19. Data showed a lower rate of clinical deterioration in patients that received colchicine compared to a standard treatment group. However, there were no differences in clinically important biomarkers reviewed.

Background: The purpose of this study was to assess the effects of colchicine, a drug commonly used to treat gout with anti-inflammatory properties, on hospitalized COVID-19 patients. The researchers collects data on clinical outcomes as well as cardiac and inflammatory biomarkers.

Methods: This study was a a prospective, open-label, randomized clinical trial, meaning that some of the patients were given colchicine and then followed. In total, 105 COVID-19 patients were included in the study, with 55 receiving colchicine and the other 50 receiving standard medical treatment. The study took place in 16 hospital in Greece from April 3rd to April 27th.

The researchers followed three variables. The first, maximum high-sensitivity cardiac troponin, is a measure of damage to heart. The second, C-reactive protein, is a measure of inflammation. The third, clinical deterioration, was calculated using a 7-grade clinical status scale, with 1 representing ability to do normal activities and 7 representing death

Results: Approximately, 14% of the patients in the control group (7 out of 50) experienced significant clinical deterioration throughout . In contrast, only 1.8% of the patients in the Colchicine group (1 out of 55) experienced significant clinical deterioration. This difference was statistically significant (P = .02).

In contrast, there was no statistically significant difference between the two groups in terms of high-sensitivity cardiac troponin and CRP.

Interpretation: This study suggests that colchicine may be helpful in reducing the rate of clinical deterioration in patient’s hospitalized for COVID-19. There was no demonstrated difference between colchicine and standard biomarkers of inflammation and heart injury. Due to the small sample size of this study, these results need further research.

Study Title: Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19

Original Article: https://jamanetwork.com/journals/jama/article-abstract/2766943

JAMA Commentary: https://jamanetwork.com/journals/jama/article-abstract/2766943

Brief Summary: Convalescent plasma serves has served a promising therapeutic option for patients with COVID-19, however, till this study there has yet to be randomized controlled trials in support of the use of convalescent plasma. In this article from JAMA, Li et al. present findings from the first randomized clinical trial of convalescent plasma therapy for patients with COVID-19 conducted in China.

Background: Convalescent plasma for the treatment of infectious diseases has been used since the early 20th century and was associated with reduced mortality in other pandemics. Several uncontrolled case series of convalescent plasma use in patients with COVID-19 have suggested a possible benefit. Given encouraging historical precedents and the absence of proven COVID-19 antiviral therapies, convalescent plasma therapy has been proposed as a treatment option. The availability of clinical information generated from randomized clinical trials is therefore of substantial importance.

Methods: In this multicenter, randomized controlled trial based in Wuhan, China 103 participants with laboratory-confirmed COVID-19 that were severe (respiratory distress and/or hypoxemia) or life-threatening (shock, organ failure, or requiring mechanical ventilation). Both groups were given either convalescent plasma in addition to standard treatment (n = 52) or standard treatment alone (control) (n = 51).

Results:  

  • Primary outcome was time to clinical improvement within 28 days, defined as a patient discharged alive or reduction of 2 points on a 6-point disease severity scale (ranging from 1 [discharge] to 6 [death]).
Outcome measuredConvalescent plasma + standard treatmentStandard treatment aloneStatistically significant
Clinical improvement in 28 days: all participants51.9% (27/52)43.1% (22/51)No 
Clinical improvement in 28 days: severe disease (respiratory distress and/or hypoxemia)91.3% (21/23)68.2% (15/22)Yes
Clinical improvement in 28 days: life-threatening (shock, organ failure, or requiring mechanical ventilation)20.7% (6/29)24.1% (7/29)No

Conclusions: Convalescent plasma use in this study was associated with some clinical improvement in severely ill patients (respiratory distress and/or hypoxemia), but not in life-threatening critically ill patients (shock, organ failure, or requiring mechanical ventilation). Greater efficacy in less ill individuals (severe disease) is expected because antibody therapies generally work best when administered earlier in disease. Lack of efficacy among patients who were in the life-threatening category, receiving mechanical ventilation and/or with some with multiorgan failure, highlights that the pathologic process in these individuals is likely irreversible.

Study Title: Remdesivir for the Treatment of Covid-19 — Preliminary Report

https://www.nejm.org/doi/full/10.1056/NEJMoa2007764?query=featured_home

Brief Summary: This study consisted of 1063 participants and was a double-blind (researchers and participants do not know if they received the drug or a placebo), randomized, placebo-controlled trial of the antiviral remdesivir in adults hospitalized with COVID-19. The primary outcome was time to recovery, which was measured by the number of days to discharge from the hospital. The researchers found patients that used Remdesivir had a lower time to recovery (11 vs. 15 days), which was statistically significant. 

Background: The purpose of this study was to determine the therapeutic effects of remdesivir in treating COVID-19 patients. Remdesivir is an antiviral that works as an inhibitor of viral RNA polymerase and has shown activity against SARS-CoV and MERS-CoV; thus, it is speculated to be a promising therapeutic candidate for COVID-19. Double blind, randomized controlled trials allow us to more definitively understand the treatment potential of Remdesivir for COVID-19.

Methods: In this multinational study, 1063 patients were randomized to remdesivir or placebo treatment. Eligible patients were randomly assigned in a 1:1 ratio to receive either remdesivir or placebo. Remdesivir was administered via IV as a 200 mg loading dose on the first day, followed by 100 mg maintenance dose administered daily on days 2 – 10 or until hospital discharge or death. A matching placebo was administered according to the same schedule and in the same volume as the active drug.  

Results: The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. 

Outcome measuredRemdesivirPlaceboStatistically significant
Recovery time (median number of days)11 days 15 days Yes 
Mortality at 14 days (%)7.1%11.9%No
Adverse Event (%) 21.1%27.0%No

Conclusions: Preliminary results of this trial suggested that a 10 day course of remdesivir was superior to placebo in reducing length of stay of hospitalized adult patients with COVID-19. Additionally, there was no increased frequency of adverse effects in patients that took remdesivir. Mortality rate at 14 days was lower in patients that took remdesevir, but this difference was not statistically significant. Future studies on Remdesevir should focus on combination therapies to assess and improve COVID-19 patient outcomes such as mortality.

Clinical Outcomes in COVID-19 Patients Treated with Tocilizumab: An Individual Patient Data Systematic Review

https://www.ncbi.nlm.nih.gov/research/coronavirus/publication/32436994

Brief Summary: Rare and severe complications of COVID-19 include Cytokine-Release Syndrome (CRS) and Macrophage Activation Syndrome (MAS). Both of these are caused by an excessive inflammatory host immune response that can induce Acute Respiratory Distress Syndrome (ARDS) and death in certain patients. Data from this study suggests Tocilizumab may be a promising treatment for COVID-induced CRS.  

Background: COVID-associated CRS/MAS are characterized by viral-induced plasma elevation of Interleukin-6, a pro-inflammatory molecule called a cytokine, which can overwhelm a patient’s immune system and induce shock, ARDS, and death. Current treatments approved for non-COVID associated CRS/MRS include a drug called Tocilizumab which inhibits the Interleukin-6 pathway thereby neutralizing the excessive host immune response. Thus, the purpose of this systematic record review was to assess if Tocilizumab is effective for controlling elevations in plasma Interleukin-6 in COVID-patients at risk for developing CRS and ARDS.   

Methods: 29 records of severely ill COVID-19 patients at risk for CRS and ARDS between the dates of April 22nd to April 27th 2020 were analyzed for baseline characteristics, lab findings, and clinical outcomes.     

Key Results: 

•IL-6 level was consistently significantly higher post initiation of Tocilizumab, supporting diagnosis of COVID-induced cytokine storm. 

•C Reactive Protein, a biological marker of inflammation, was consistently significantly decreased post Tocilizumab treatment compared to baseline.  

Conclusion: Based on the results, the researchers suggest that treatment with Tocilizumab in high risk COVID-19 patients with significantly high Interleukin-6 plasma levels significantly reduces the hyper-inflammatory state caused by the overactive Interleukin-6 pathway, thus decreasing risk of CRS and ARDS. It is unknown if Tocilizumab therapy significantly impacts mortality rates, and more research is needed for further evaluation of the drug.

Study Title: Case-Fatality Rate and Characteristics of Patients Dying in Relation to Covid-19 in Italy (From the Journal of American Medical Association) 

https://jamanetwork.com/journals/jama/fullarticle/2763667

Brief Summary: As of 03/27, Italy is the country with the highest COVID-19 fatality rate and 3rd highest total number of cases. This study outlines three possible reasons why Italy has a high COVID-19 fatality rate: elderly population, a broader definition of COVID-19 death, and testing focused on sicker patients. 

Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1

https://www.nejm.org/doi/full/10.1056/NEJMc2004973

Brief Summary: COVID can be passed through aerosol and surface transmission because of its ability to remain viable and infectious. However, this does not mean that you should refrain from going outside around your house. It is important to note that though transmission through surfaces does not occur as often as through aerosol droplets, cleaning surfaces can minimize risk of transmission. 

Inhibitors and Angiotensin Receptor Blockers: What is the Evidence? (From the Journal of American Medical Association)

https://jamanetwork.com/journals/jama/fullarticle/2763803

Brief Summary: There is speculation that two classes of medications used to treat diabetes and hypertension, called ACE Inhibitors (ACE-Is) and Angiotensin Receptor Blockers (ARBs), may increase vulnerability to COVID-19 infection. However, there is no clinical data to suggest this, and patients should continue to take these medications as prescribed unless told otherwise by their doctor. 

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