COVID-19: Expert Review of Relevant and Emerging Literature

COVID-19: Expert Reviews of Relevant and Emerging Literature2020-05-29T11:40:37-04:00
Published on :  | By Maria Brann

Review: How you should read coronavirus studies, or any science paper

This column points out the difficulty in reading scientific papers and offers suggestions for understanding this type of manuscript (which provides insight for what researchers should do to help readers).

After a brief history of how scientific writing has evolved, the author argues that researchers can tell the story of their study orally better than in writing and thus, readers must decipher what is written. It is important to understand how an article is set up: history or justification for the study, methods used to do the study, results, and discussion of what the results mean. After knowing the format, one should read through the paper with a healthy skepticism because much of the research published about COVID-19 is in preprint format, which means that it has not been peer-reviewed. Even when it has, mistakes can be made and therefore, healthy skepticism allows the reader to evaluate the merit of the research. A recommended shortcut is to follow leading epidemiologists and virologists on social media because they often post what is good or bad about emerging research. Experts are encouraged to tell the story of their research in easy to understand ways, including using social media to highlight important findings.

 

The authors of this paper argue that advance care planning and discussing goals of care are of heightened importance  for patients with chronic, life-limiting disease, due to COVID-19 for three reasons:

1) It is an ethical imperative to avoid providing unwanted life-sustaining interventions; 2) avoiding unwanted or non-beneficial treatments will alleviate stress on the health care system; and 3) providing unwanted or non-beneficial treatment puts others at risk due to the potential transmission of COVID-19.  For all these reasons, clinicians should prioritize proactive advance care planning. The authors provide guidance on the logistics of engaging in goals of care discussions, with specific discussion about code status or the use of CPR and advanced cardiac life support (ACLS), and the use of do-not-resuscitate (DNR) orders. The implementation of informed assent, in which the provider asks the patient or family member to allow the clinician to assume responsibility for the care decisions, “may be useful for patients in whom CPR is exceedingly unlikely to allow a successful return to a quality of life they would find acceptable.”  The Informed Assent Framework,  is implemented when family members allow the clinician to make decisions as they are unable or unwilling got accept responsibility themselves, because of the psychological burden the decision places on them.

Curtis, J. R., Kross, E. K., & Stapleton, R. D. (2020). The importance of addressing advance care planning and decisions about do-not-resuscitate orders during novel coronavirus 2019 (COVID-19). Jama.

This modeling study explored different interventions (not involving medications/vaccines) influencing new cases and deaths related to COVID-19 and found that intermittent periods of more intensive lockdown-type measures may be necessary to prevent healthcare systems from being overwhelmed. 

  • The model explored a range of intervention scenarios, tracking approximately 65 million people in England, Wales, Scotland, and Northern Ireland
  • The four base interventions modeled included: school closures, physical distancing, shielding of people aged 70 years+, and self-isolation of symptomatic cases
    • A combination of these interventions was also modeled
    • These interventions were also modeled with more intensive interventions, such as phased lockdown-type restrictions for multiple periods
  • Each of the 4 base interventions were likely to decrease R0, but not enough to prevent ICU demand from exceeding health service capacity
  • Only lock-down periods were sufficient to bring R0 near or below 1, with the most stringent lockdown scenario projected to result in an estimated 120,000 cases (46,000–700,000) and 50,000 deaths (9,300–160,000)

This observational study found that half of the patient with negative IgM and RT-qPCR-positive SARS-CoV-2 had severe COVID-19 disease. 

  • IgM-based gold immunochromatographic assay (GICA) is the test used within this study, to investigate its utility
  • Severe cases were defined as patients requiring ICU level care and receiving treatment for 3 days.
  • The IgM-GICA positivity from the RT-qPCR confirmed COVID-19 patients is shown to be 82.2% (37/45)
  • Specificity testing of IgM-GICA did not detect SARS-CoV-2 antibodies in human sera infected with other viruses or from healthy people
  • IgM detection rates were substantially lower in patients who progressed to severe disease as opposed to mild disease:
  • At 4–7 days after symptom onset, the positive rate of the mild group was 64% (16/25), compared to 16.7% (1/6) in the severe group
  • At 15–21 days after symptom onset, the positive rate of the mild group was 100% (15/15), compared to 75% (6/8) in the severe group

This case series described 3 patients with typical Guillain-Barre Syndrome preceded by symptoms of (and biologically confirmed) COVID-19, with neurological symptoms appearing within the first 22 days of COVID-19 symptoms. 

  • Patients from Geneva and Lausanne University Hospitals, Switzerland, between March and April 2020
  • All patients presented with distal paresthesias and rapidly progressive limb weakness, evolving to either moderate tetraparesis (n =2) or tetraplegia (n=1) and areflexia (n=3) within the first five days.
  • All showed classic demyelinating pattern
  • One required mechanical ventilation
  • Neurological symptoms appeared  at 7, 15 and 22 days after the appearance of typical COVID-19 related symptoms
  • Initial RT-PCR swab +SAR-CoV-2 on initial swab for two patients, third patient showed seroconversion and a 4th swap was positive.
  • All received IVIG
  • One patient was discharged, one now walks with assistance, the third is bed-bound but can rise to stand up.

This case series found hospitalized pediatric patients infected with COVID-19 were significantly younger; more likely to have an underlying comorbidity or coinfection, and more likely to report fever and dyspnea, compared to non-hospitalized COVID-19 pediatric patients. Pediatric patients also likely to have a COVID-19 infected adult within their household. 

  • Study involved COVID-19 patients living in Chicago aged 0-17 years, who were reported to Chicago Department of Public Health (CDPH) from 3/5/20–4/8/20.
  • 6369 lab-confirmed cases of COVID-19 were reported, with only 64 (1.0%) were among children 0-17 years.
    • 10 patients (16%) were hospitalized
      • 7 (70%) required ICU
      • Of those hospitalized, all had an underlying comorbidity or co-infection
      • median length of hospitalization 4 days (range: 1–14).
  •  Among the 34 unique households with multiple laboratory-confirmed infections, median number of laboratory-confirmed infections was 2 (range: 2–5)
  • 2 (7%) had traveled to NYC within prior 14 days
  • 40 (64%) of children had at least one family member with COVID-19
  • 15 households with available data to assess transmission (transmission defined as one individual testing positive prior to another individual, which has limitations)
    • 11 (73%) were adult-to-child, 2 (13%) child-to-child, and 2 (13%) child-to-adult.

 

Published on :  | By Laramie Mack

Review: COVID-19 and older adults: What we know

This is an overview of COVID-19 in older adults, who are more likely to be infected with the virus and have worse outcomes of COVID-19.

  • Pathophysiology: Angiotensin-converting enzyme-2 (ACE-2) receptor may be a mechanism for cell entry. Since a large portion of older adults have comorbidities such as hypertension and chronic kidney disease (CKD) and these diseases are often treated with ACE-2 inhibitors and angiotensin-receptor blockers which upregulate the ACE-2 receptor the older adult population may have an increased risk of infection along with more severe symptoms once the infection is present. (Note: This potential mechanism is being studied and the American Heart Association has made a statement that patients should not be taken off ACEI or ARBs until more information is known.)
  • Clinical Presentation: Common symptoms in older adults include shortness of breath, fever, and cough. Older adults who survive infection are often left with organ damage due to acute respiratory disease syndrome, acute kidney injury, cardiac injury, and liver dysfunction. Chest imaging may reveal bilateral lower lung involvement, ground glass opacities, and even pleural effusions among other potential findings.
  • Mortality: Many studies have shown higher rates of mortality in older adults, especially in those over 80. At the time of this article’s publication 80% of COVID-19 deaths were in individuals over the age of 65. Comorbidities also result in an increase in mortality rates. Multiple studies have found increased mortality rates in diseases often associated with older adults such as diabetes, congestive heart failure, COPD, and CKD.
  • Treatment: Good hand hygiene, social distance, and personal protective equipment have helped with preventing spread of the disease. Supportive care is currently the main goal of treatment as there are currently no FDA-approved treatments. There are, however, treatment options being tested. Chloroquine, hydroxychloroquine, and remdesivir are all currently being trial both in and outside of the United States. There is also currently a phase I trial of a potential vaccine. It is recommended that all of those who eligible receive the influenza vaccine to prevent influenza and unnecessary evaluation for SARS-CoV-2.

This study compared 4 commercial ELISAs and 2 rapid tests for detecting antibodies in individuals with PCR-confirmed SARS-CoV-2 infection and found that while test sensitivities were low within the first 5 days, by >10 days, all evaluated tests provided positive results >10 days post disease onset. 

  • Compared tests:
    • Four ELISAs – Euroimmun SARS-CoV-2 IgA and IgG, Wantai SARS-CoV-2 IgM and total antibodies
    • Two rapid tests (Wantai SARS-CoV-2 Ab Rapid Test and 2019-nCoV IgG/IgM Rapid Test)
  • Serum or plasma from 77 symptomatic patients with acute SARS-CoV-2 infection, who were diagnosed by positive PCR were used
  • Serum samples from 100 indivdiuals without SARS-CoV-2 served as controls
  • Sensitivities were low (<40%) within the first 5 days post disease onset, IgM-, IgA- and total antibody-ELISAs increased in sensitivity to >80% between the 6th and 10th day post symptom onset. The evaluated tests (including IgG and rapid tests) provided positive results in ALL patients >10th day post onset of disease.
  • Specificities were 83% and 98% for the Euroimmun IgA and IgG and 97% for the Wantai IgM and the Ab ELISAs, respectively
  • The Wantai Rapid Test displayed a specificity of 98%, and the 2019-2019-nCoV IgG/IgM Rapid Test 100% for IgM and IgG respectively

This small observational study found trough concentration in critically ill patients was much lower than that of healthy subjects in a previous clinical trial. This is cause for further pharmacokinetic research regarding optimal dosage and formulation for critically ill patients. 

  • The patients were administered 1600 mg of facipiravir twice daily on Day 1, followed by 600 mg twice daily from Day 2 to Day 5 (or more if needed). Trough levels were obtained
  • The clinical status after starting facipiravir was evaluated on Day 1–5, Day 7, and Day 14 by a seven-category ordinal scale
  • Seven patients were enrolled in this study. Forty‐nine blood samples were obtained these patients for the study
  • Although some improvement was observed in three patients with COVID-19 by Day 14, it is unclear how facipiravir influenced this improvement. (Sample size was very limited)
  • The facipiravir trough (after 8–12 h) concentrations of most samples (multiple samples for 5 of the 7 patients) were lower than the lower limit of quantification (1 µg/mL) and EC50 (9.7 µg/mL) against SARS‐CoV‐2 previously tested in vitro .

In this study, the diagnosis of influenza-like illness trends with both influenza (which was decreasing up until March) and COVID-19  (which began sharply increasing in March). In 3 of the 4 regions of New York State (not including NYC), the diagnoses of ILI increased ahead of the emergence of COVID-19.

  • Influenza-like illness (ILI) is defined as fever of 100°F or greater with cough and/or sore throat in the absence of another known cause
  • Used two sources for data:
    • Outpatient Influenza-like Illness Surveillance Network (ILINet)- For ILI prevalence
    • NY State Department of Health database- influenza types A-B and SARS-CoV-2 tests from state-wide laboratories are reported to this database
  • Until the emergence of COVID-19 in early March, ILI and laboratory-confirmed influenza tracked closely together, with both declining.
  • Afterwards, in the Metropolitan region of NYS region, with the highest rates of confirmed COVID-19, ILI increased most sharply.
  • In the other three regions, ILI increased ahead of the emergence of COVID-19. This might signal early COVID-19 activity without diagnosis in those regions or increased concern over COVID-19 and care-seeking among people with mild ILI

This population-based, observational study assessed the incidence and outcomes of out-of-hospital cardiac arrest (OHCA) in an urban region (Paris, France) during the COVID-19 pandemic, compared with non-pandemic periods.

The authors examined data for non-traumatic OHCA (N=30,768) and evaluated OHCA incidence and outcomes over a 6-week period during the pandemic in adult inhabitants of the study area.

They identified 521 OHCAs during the pandemic period (March 16-April 26, 2020) and 3052 total OCHAs occurring in the same weeks during the non-pandemic period (years 2012-2019). When comparing these periods, they found that the maximum weekly OHCA incidence increased from 13.42 (95% CI 12.77–14.07) to 26.64 (25.72–27.53) per million inhabitants (p<0.0001), before returning to normal in the final weeks of the pandemic period.

Patient demographics did not change substantially during the pandemic compared with the non-pandemic period. On the other hand, there was a higher rate of OHCA at home (460 [90.2%] vs 2336 [76.8%]; p<0·0001), less bystander cardiopulmonary resuscitation (239 [47.8%] vs 1165 [63.9%]; p<0·0001) and shockable rhythm (46 [9.2%] vs 472 [19.1%]; p<0·0001), and longer delays to intervention (median 10.4 min [IQR 8.4–13.8] vs 9.4 min [7.9–12.6]; p<0.0001) during the pandemic period. In addition, the proportion of patients who had an OHCA and were admitted alive decreased from 22.8% to 12.8% (p<0·0001).

After adjustment for potential confounders, the pandemic period remained significantly associated with lower survival rate at hospital admission (odds ratio 0.36, 95% CI 0.24–0.52; p<0.0001). COVID-19 infection, confirmed or suspected, accounted for approximately a third of the increase in OHCA incidence during the pandemic.

This rapid evidence review determined that people vary widely in their adherence to quarantine recommendations and provides recommendations for public health officials to improve compliance.

Because adhering to quarantine can be difficult, the researchers wanted to assess what factors contribute to greater compliance with self-isolation recommendations. They found that adherence was mainly associated with knowledge, social norms, perceived benefits and risks, and practical influences. To increase the likelihood of individuals adhering to guidelines during the COVID-19 pandemic, the researchers urge public health officials to disseminate timely, clear information about what to do and why to do it. They also note that it is important to emphasize altruistic social norms, increase understanding of the benefit to not only oneself but also to others, and ensure essential food and medication are accessible.

This perspective suggests integrating risk communication and community engagement to address the COVID-19 pandemic.

By studying the communication in China during the COVID-19 outbreak, scholars provide suggestions for improving emergency responses. These include improvements to internal governmental risk communication systems, enhancing coordination between internal and partner governmental emergency management, and promoting public communication in response to societal concerns. The authors also stress the necessity of community engagement to prevent and control the outbreak. It is important that communication addresses uncertainty, counters misinformation effectively, and reflects evidence-based decision-making practices.

 

This study projected the number of excess suicides in Canada as a consequence of the impact of COVID-19 on unemployment.

The authors derived annual suicide mortality (2000-2018) and unemployment (2000-2019) data from Statistics Canada and used time-trend regression models to evaluate and predict the number of excess suicides in 2020 and 2021 for two possible projection scenarios following the COVID-19 pandemic: 1) an increase in unemployment of 1.6% in 2020, 1.2% in 2021, or 2) an increase in unemployment of 10.7% in 2020, 8.9% in 2021.

They found that in the first scenario, the rise in unemployment rates would result in a projected total of 418 excess suicides in 2020-2021 (suicide rate per 100,000: 11.6 in 2020). In the second scenario, the projected suicide rates per 100,000 increased to 14.0 in 2020 and 13.6 in 2021, resulting in 2114 excess suicides in 2020-2021.

Their findings indicate that suicide prevention in the context of COVID-19-related unemployment may be critical. They propose timely access to mental healthcare, financial provisions and social/labor support programs, as well as optimal treatment for mental disorders.

It is urgent to understand the future of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) transmission. This study used estimates of seasonality, immunity, and cross-immunity for human coronavirus OC43 (HCoV-OC43) and HCoV-HKU1 using time-series data from the United States to inform a model of SARS-CoV-2 transmission.

The authors projected that recurrent wintertime outbreaks of SARS-CoV-2 will probably occur after the initial, most severe pandemic wave. Absent other interventions, a key metric for the success of social distancing is whether critical care capacities are exceeded. To avoid this, they believe that prolonged or intermittent social distancing may be necessary into 2022. They proposed additional interventions, including expanded critical care capacity and an effective therapeutic, to improve the success of intermittent distancing and hasten the acquisition of herd immunity.

Finally, they underscore the urgent need for longitudinal serological studies to determine the extent and duration of immunity to SARS-CoV-2. They believe that SARS-CoV-2 surveillance should be maintained even in the event of apparent elimination because a resurgence in contagion could be possible as late as 2024.

This study reports on hospitalization and mortality among black and white patients with COVID-19. Using retrospective cohort data from Louisiana, the authors found an excess risk of hospitalization for COVID-19 among black patients versus white patients, which was not explained by comorbidities or obesity. In terms of mortality, 70.6% of patients who died were black (versus 31% of the cohort), but black race was not associated with higher in-hospital mortality than white race after accounting for differences in sociodemographic and clinical characteristics on admission.

The authors examined 3481 patients seen within an integrated-delivery health system (Ochsner Health) in Louisiana between March 1 and April 11, 2020, who tested positive for SARS-CoV-2 on qualitative polymerase-chain-reaction assay.

Of the 3481 Covid-19–positive patients:

  • 60.0% were female
  • 70.4% were black non-Hispanic
  • 29.6% were white non-Hispanic
  • Black patients had higher prevalences of obesity, diabetes, hypertension, and chronic kidney disease than white patients
  • 39.7% of Covid-19–positive patients (1382 patients) were hospitalized, 76.9% of whom were black
  • Among the 326 patients who died from Covid-19, 70.6% were black.

In multivariable analyses, black race, increasing age, a higher score on the Charlson Comorbidity Index (indicating a greater burden of illness), public insurance (Medicare or Medicaid), residence in a low-income area, and obesity were associated with increased odds of hospital admission.

In adjusted time-to-event analyses, variables that were associated with higher in-hospital mortality were increasing age and presentation with an elevated respiratory rate; elevated levels of venous lactate, creatinine, or procalcitonin; or low platelet or lymphocyte counts. However, black race was not independently associated with higher mortality (hazard ratio for death vs. white race, 0.89; 95% confidence interval, 0.68 to 1.17).

This Viewpoint compares manual and digital strategies for coronavirus disease 2019 (COVID-19) contact tracing, describes how countries in Asia and Europe have used smartphone tracking, and discusses privacy and discrimination concerns and strategies for balancing public health and civil liberties in the US.

The authors note that the best uses of digital (e.g., smartphone) technologies augment, but do not replace, manual tracing. They point to successful strategies in Maryland, Massachusetts, and New York that have massively scaled up manual tracing approaches by automating systems. However, they also find value in digital tracing approaches to significantly contribute to curtailing the spread of SARS-CoV-2 infection if adopted widely and integrated into comprehensive public health strategies. The discuss an Apple-Google system that could rapidly notify smartphone users if they have been in close proximity with a person medically diagnosed with COVID-19. They believe that it is important for public health agencies to have oversight of such systems, and note that the voluntary nature of downloading and using this type of smartphone application means that widespread uptake will be required for the system to be most effective.

They also discuss two contrasting approaches to digital contact tracing: a more centralized approach favored by governments in China, South Korea, Taiwan, and elsewhere and a decentralized, user-centric approach supported by the joint Apple-Google system and favored by some, but not all, European countries.

In their opinion, the optimal design for a digital tracing system could balance health and privacy. They believe that digital tracing should augment traditional public health strategies but not replace them.

Published on :  | By Aaron Carroll

ICYMI – The COVID-19 week in review (May 29, 2020).

This will be an ongoing, weekly post that will highlight the things you should have read (at least in MY opinion).

Articles you might have missed:

  1. About a dozen states report upticks in new cases as the U.S. outlook improves.
  2. Hunger Program’s Slow Start Leaves Millions of Children Waiting, by Jason DeParle.
  3. So, What Can We Do Now? A guide to staying safe this summer, by Amanda Mull.
  4. Americans Aren’t Getting the Advice They Need, by Julia Marcus.
  5. The World Is Still Far From Herd Immunity for Coronavirus, by Nadja Popovich and Margot Sanger-Katz. Look at the charts.

What I’m writing:

What I’m reading:

This research article determined that mass media and peer educators are the predominant source of COVID-19 information for health care professionals.

The findings from this study of medical professionals, medical students, and community workers in Vietnam suggest that mass media and peer educators are the information channels most frequently used for information about COVID-19. This reinforces the importance of the role of mass media and health professionals in disseminating timely and accurate information found in studies in other countries including the United States. With the quickly changing policies and regulations of COVID-19 prevention and control, it is imperative that health care professionals have access to the most up-to-date information, which they would likely access through mass media or peers. The researchers argue that results from this study provide evidence for urgently formulating or re-designing training programs and communication activities to enhance the capacity of the health care personnel who are rapidly responding to the COVID-19 pandemic.

This cross-sectional study found a substantial proportion of mental health issues in healthcare workers (HCWs) during the pandemic, particularly among women and front-line healthcare workers. 

  • Cross-sectional, web-based study collected data between March 27 and March 31, 2020 (days immediately preceding the COVID-19 peak in Italy), using an online questionnaire spread via social networks using a snowball technique and sponsored social network advertisements, making it impossible to determine response rate.
  • Key mental health outcomes were posttraumatic stress symptoms (PTSS), symptoms of depression, anxiety, insomnia, and perceived stress were assessed.
  • A total of 1379 HCWs completed the questionnaire
    • 49.38% endorsed PTSS
    • 24.73% endorsed symptoms of depression
    • 19.80% endorsed symptoms of anxiety
    • 8.27% endorsed insomnia
    • 21.90% endorsed high perceived stress
  • Having a colleague deceased was associated with PTSS (OR, 2.60; 95% CI, 1.30-5.19; P = .007) and symptoms of depression (OR, 2.07; 95% CI, 1.05-4.07; P = .04) and insomnia (OR, 2.94; 95% CI, 1.21-7.18; P = .02)
  • Having a colleague hospitalized was associated with PTSS (OR, 1.54; 95% CI, 1.10-2.16; P = .01) and higher perceived stress (OR, 1.93; 95% CI, 1.30-2.85; P = .001)
  • Being exposed to contagion was associated with symptoms of depression (OR, 1.54; 95% CI, 1.11-2.14; P = .01)
COVID-19 Digest Links
Creative Commons License The literature reviews on this blog were created under a Creative Commons Attribution-NonCommercial 4.0 International License , which allows the reuse and adaptation of the work by noncommercial entities. These rights do not extend to the articles that the authors are reviewing.
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