COVID-19 Science Update released: May 26, 2020 Edition 16

COVID-19 Science Update

From the Office of the Chief Medical Officer, CDC COVID-19 Response, and the CDC Library, Atlanta GA. Intended for use by public health professionals responding to the COVID-19 pandemic.

*** Available on-line at http://www.cdc.gov/library/covid19 ***

 

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COVID-19 Science Updates

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Modeling & Transmission: Bending the Curve

In the absence of a vaccine and therapeutics, population-based policies remain critical to reduce COVID-19 transmission. Social distancing has previously been used to slow the spread of communicable diseases, and science on the importance of this population-based policy in the context of SARS-CoV-2 continues to grow. The following two studies shed light on this topic.

PEER-REVIEWED

Cluster of coronavirus disease associated with fitness dance classes, South Korea. Jang et al. Emerging Infectious Diseases (May 15, 2020).

Key findings:

  • Of 217 adult students who participated in high-intensity aerobic dance classes across 12 facilities, 57 (26%) were infected with SARS-CoV-2 from contact with instructors.
  • Classes where transmission occurred typically included 5–22 people in a 645 square-foot room (about the size of a 3-car garage) for 50 minutes.
    • No cases observed in classes with <5 participants.
  • No students who took low-intensity classes (Pilates and yoga) from an infected instructor tested positive for SARS-CoV-2.

Methods: Contact tracing study in Cheonan, South Korea from February 15 to March 9, 2020. Limitations: Unclear whether any transmission occurred from instructors while presymptomatic.

 

Strong social distancing measures in the United States reduced the COVID-19 growth rateexternal icon. Courtemanche et al. Health Affairs (May 14, 2020).

Key findings:

  • A combination of 4 social distancing measures in the US reduced the COVID-19 daily growth rate by 5% after 1–5 days, 7% after 6–10 days, 8% after 11–15 days, and 9% after 16–20 days.
  • Without implementation of these measures, modelers estimated that COVID-19 cases would have been about 35 times higher than the observed number on April 27, 2020 (35,257,098 vs 978,047).
  • Shelter in place orders and the closure of restaurants, bars, gyms, or other entertainment centers were the most effective measures to reduce the case growth rate compared with bans on large social gatherings (500+ people) and public school closures (Figures 1 & 2).

Methods: Analysis of the daily confirmed COVID-19 case growth rate in all US counties after the implementation of four government-imposed social distancing measures between March 1 and April 27, 2020. The model used event-study regression with multiple treatments and fixed effects for population density and resident’s education, political orientation, and age. Limitations: Underestimation of asymptomatic and mild cases and those not able to be tested; differences in case reporting practices by county were not accounted for in the model.

Figure 1

Figure 2

Note: Adapted from Courtemanche et al. Estimates of COVID-19 case growth rate change before and after the implementation of four government imposed social distancing measures. Figure 1: shelter in place order compared with bans on large gatherings. Figure 2: restaurant, bar or other entertainment center closure compared with public school closure. Used by permission from publisher.

Implications of 2 studies (Jang et al. & Courtemanche et al.): Social distancing measures can slow SARS-CoV-2 transmission. As restrictions are relaxed, it will be important to monitor possible transmission during various activities, including high-intensity aerobic exercise in enclosed spaces, even in small groups.

Clinical Treatment & Management

PEER-REVIEWED

Use of prone positioning in nonintubated patients with COVID-19 and hypoxemic acute respiratory failureexternal icon. Elharrar et al. JAMA (May 15, 2020).

Key findings:

  • Among 24 hospitalized, nonintubated COVID-19 patients requiring oxygen, 15 (63%) tolerated face-down (prone) positioning for >3 hours.
  • 6 (25%) patients had ≥20% increase in oxygen level during prone positioning (Responders) (Figure).
    • 3 (13%) had a persistent increase in oxygen level after being returned to the face-up position for 6–12 hours (Persistent Responders).

Methods: Prospective, single-hospital study of 24 patients with COVID-19 who required oxygen, but not intensive care. Oxygen level measured before, during, and after prone positioning. Response to prone positioning defined as ≥20% increase in partial pressure of arterial oxygen (PaO2). Limitations: Single center; small sample.

Implications: Prone positioning is commonly used for intubated, sedated patients and may benefit a subset of non-intubated COVID-19 patients. Further research on this issue is needed, and a clinical trial is underway.

Figure:

Note: Adapted from Elharrar et al. Individual partial pressure of arterial oxygen (Pa02) variation among patients who sustained prone positioning for >3 hours. Responders had a Pa02 increase ≥20% during prone positioning. Persistent responders maintained a PaO2 increase ≥20% at least 6-12 hours after completing prone positioning. Nonresponders had a Pa02 increase <20% during prone positioning. Reproduced with permission from JAMA. doi:10.1001/jama.2020.8255. Copyright©2020 American Medical Association. All rights reserved.

Immunity Against Reinfection

B cells and T cells protect the body from repeated attacks by pathogens, including viruses. B cells make antibodies that coat viruses and neutralize their ability to infect cells. T cells recognize infected cells and either kill the cell (killer T cells) or help other immune cells fight infection (helper T cells). However, little is known about the human immune response to SARS-CoV-2. The following four studies shed light on this topic.

PREPRINT (NOT PEER-REVIEWED)

A. Convergent antibody responses to SARS-CoV-2 infection in convalescent individualsexternal icon. Robbiani et al. bioRxiv (May 22, 2020). Publishedexternal icon in Nature (June 18,2020).

Key findings:

  • Blood samples from 149 COVID-19 patients contained varying levels of antibodies able to neutralize virus and protect cells from infection with SARS-CoV-2.
  • Neutralizing activity was strongest in patients who recovered from severe COVID-19.

Methods: Blood was collected from 149 people who had recovered from COVID-19, an average of 39 days after onset of symptoms and ≥14 days after symptom resolution. Antibodies reactive against SARS-CoV-2 were quantified with ELISA. Neutralizing activity was measured with pseudotyped virus assays. Limitations: Laboratory study; in vivo immunity against reinfection in patients recovered from COVID-19 not assessed.

PEER-REVIEWED

B. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individualsexternal icon Grifoni et al. Cell (May 14, 2020).

Key findings:

  • Among 10 people who recovered from COVID-19, 7 (70%) had killer T cells and 10 (100%) had helper T cells specific to SARS-CoV-2, including the viral spike protein.
  • 6 of 11 (55%) unexposed healthy controls also had SARS-CoV-2-specific helper T cells, consistent with cross-reactive T cell recognition possibly from prior infection with “common cold” coronaviruses.

Methods: Blood was collected from 20 adults who had recovered from COVID-19, 20–35 days after symptom onset and ≥14 days after symptom resolution. T helper and killer cells in samples from recovered COVID-19 patients and 11 healthy donors (collected before the COVID-19 pandemic) were tested for reactivity to SARS-CoV-2. Limitations: Small sample size; laboratory study; in vivo immunity to reinfection with SARS-CoV-2 not assessed.

 

PREPRINT (NOT PEER-REVIEWED)

C. Presence of SARS-CoV-2-reactive T cells in COVID-19 patients and healthy donorsexternal icon. Braun et al. medRxiv (April 22, 2020). Publishedexternal icon in Nature (July 29, 2020).

Key findings:

  • 15 of 18 (83%) COVID-19 patients with varying disease severity and 23 of 68 (34%) SARS-CoV-2 seronegative healthy donors had helper T cells specific to SARS-CoV-2; the latter finding may be consistent with cross-reactive T cell recognition from prior infection with “common cold” coronaviruses.

Methods: Helper T cells in blood samples collected from 18 patients with mild to critical COVID-19 and 68 healthy controls were tested for reactivity to SARS-CoV-2 spike protein. Limitations: Presence of killer T cells not determined; time from symptom onset to sampling (time available to mount an immune response) was shorter for COVID-19 patients with critical compared with mild or moderate disease (range 2–11 vs 5–39 days).

PEER-REVIEWED

D. SARS-CoV-2 infection protects against rechallenge in rhesus macaquesexternal icon. Chandrashekar et al. Science (May 20, 2020).

Key findings:

  • 9 rhesus macaques inoculated with SARS-CoV-2 developed pneumonia, high viral loads, neutralizing antibody, and cellular immunity.
    • All 9 rhesus macaques recovered.
  • Upon rechallenge, the animals exhibited a robust increase in SARS-CoV-2-specific antibodies with rapid clearance of virus (Figure).

Methods: 9 rhesus macaques (monkeys) infected with SARS-CoV-2; humoral and cellular immune responses were examined; on day 35, all were rechallenged. Limitations: There are differences between SARS-CoV-2 infection in rhesus macaques and humans (e.g., rhesus macaques do not develop respiratory failure or die from SARS-CoV-2 infection); studies are needed to determine if SARS-CoV-2 infection leads to subsequent immunity in humans.

Figure:

Note: Adapted from Chandrashekar et al. Comparison of viral RNA from lung fluid following initial infection and rechallenge. Red bar is median viral load. Licensed under CC-BY 4.0.

 

Implications of 4 studies (Robbiani et al., Grifoni et al., Braun et al. & Chandrashekar et al.): Most people with COVID-19 develop neutralizing antibodies and helper T cells specific for SARS-CoV-2 that may help prevent reinfection. Similar defenses prevented reinfection of rhesus macaques with SARS-CoV-2. Studies are underway to ascertain whether a similar protective effect of natural infection with SARS-CoV-2 occurs in humans, which can help inform vaccine development.

COVID-19 and the GI System

The gastrointestinal (GI) system is often affected during COVID-19. The following two articles provide insight about the predictive value of combinations of symptoms and the prevalence of GI complications.

PEER-REVIEWED

Are gastrointestinal symptoms specific for COVID-19 infection? A prospective case-control study from the United Statesexternal icon. Chen et al. Gastroenterology (May 12, 2020).

Key findings:

  • GI symptoms were more common among people who tested positive (74%) than negative (53%) for SARS-CoV-2.
  • Combinations of symptoms were more predictive of COVID-19 than individual symptoms, with specificities (ability to correctly identify those without the disease) of 94%-99%.
    • 88% of those with a combination of 5 symptoms (fever, diarrhea, loss of smell, taste, & appetite) tested positive for SARS-CoV-2; however, this suite of symptoms was seen in only one-quarter of people with confirmed COVID-19 (n = 24) (Figure).

Methods: Telephone survey of 340 adults tested for SARS-CoV-2 by NP swab RT-PCR (positive, 101; negative, 239) in one hospital; determined likelihood of combinations of COVID-19-related symptoms to predict presence (positive predictive value) or absence (negative predictive value) of infection with SARS CoV-2. Limitations: Timing of symptoms in relation to testing and diagnosis was unclear; mostly outpatients with mild to moderate symptoms.

Figure:

Note: Adapted from Chen et al. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of combinations of GI and non-GI symptoms for COVID-19. Each colored row denotes a different symptom.  This article was published in Gastroenterology, Vol 159, Chen et al., Are gastrointestinal symptoms specific for COVID-19 infection? A prospective case-control study from the United States, Page 1161-1163.e2, Copyright the AGA Institute 2020. This article is currently available at the Elsevier COVID-19 resource center: https://www.elsevier.com/connect/coronavirus-information-centerexternal icon.

 

Gastrointestinal complications in critically ill patients with COVID-19external icon. Kaafarani et al. Annals of Surgery (May 1, 2020).

Key findings:

  • 45% of 141 COVID-19 ICU patients had GI symptoms (e.g., abdominal pain, diarrhea, vomiting) on admission and 104 (74%) developed at least one GI complication while hospitalized, of whom:
    • 67% had abnormal liver function tests.
    • 56% had intestinal paralysis, 5% needed surgery, 3% had patches of dead bowel with SARS-CoV-2-induced small vessel thrombosis or bowel nerve injury proposed as possible causes of the injury (Figure).

Methods: 141 ICU patients with SARS-CoV-2 infection between March 13 and April 12, 2020 at one hospital in Massachusetts. Limitations: Case series; drug effects and metabolic and electrolyte disturbances in critically ill patients may have contributed to the findings.

Figure:

Picture showing that the necrotic bowel had a distinct bright yellow color in contrast to the common finding of purple-black color

Note: from Kaafarani et al.  (Supplementary Appendixexternal icon) Diffuse yellowish areas of dead small bowel and colon. Available via Wolters Kluwer Public Health Emergency Collection through PubMed Central.

Implications of both studies (Chen et al. & Kaafarani et al.): Clinicians can recognize COVID-19 earlier, and respond appropriately to adverse events, by being alert to common GI symptoms and complications that have occurred among COVID-19 patients.

In Brief

Disclaimer: The purpose of the CDC COVID-19 Science Update is to share public health articles with public health agencies and departments for informational and educational purposes. Materials listed in this Science Update are selected to provide awareness of relevant public health literature. A material’s inclusion and the material itself provided here in full or in part, does not necessarily represent the views of the U.S. Department of Health and Human Services or the CDC, nor does it necessarily imply endorsement of methods or findings. While much of the COVID-19 literature is open access or otherwise freely available, it is the responsibility of the third-party user to determine whether any intellectual property rights govern the use of materials in this Science Update prior to use or distribution. Findings are based on research available at the time of this publication and may be subject to change.

 

Page last reviewed: January 7, 2021
Content source: Office of the Chief Science Officer - COVID-19