SARS-CoV-2

Background
To evaluate the duration of protection against reinfection conferred by a previous SARS-CoV-2 infection in children and adolescents.
Methods
We applied two complementary approaches: a matched test-negative, case-control design and a retrospective cohort design. 458,959 unvaccinated individuals aged 5-18 years were included. Analyses focused on July 1 to December 13, 2021, a period of Delta variant dominance in Israel. We evaluated three SARS-CoV-2-related outcomes: documented PCR confirmed infection or reinfection, symptomatic infection or reinfection, and SARS-CoV-2-related hospitalization or death.
Findings
Overall, children and adolescents who were previously infected acquired durable protection against reinfection with SARS-CoV-2 for at least 18 months. Importantly, no SARS-CoV-2-related deaths were recorded in either the SARS-CoV-2 naïve group or the previously infected group. Effectiveness of naturally-acquired immunity against a recurrent infection reached 89.2% (95% CI: 84.7%-92.4%) three to six months after first infection, mildly declining to 82.5% (95% CI, 79.1%-85.3%) 9-12 months after infection, with a slight non-significant waning trend up to 18 months after infection. Additionally, we found that ages 5-11 years exhibited no significant waning of naturally acquired protection throughout the outcome period, whereas waning protection in the 12-18 year-old age group was more prominent, but still mild.
Interpretation
Children and adolescents who were previously infected with SARS-CoV-2 remain protected to a high degree for 18 months. Further research is needed to examine naturally-acquired immunity against Omicron and newer emerging variants.

Author/s:

Patalon, T., Saciuk, Y., Perez, G., Peretz, A., Ben-Tov, A., Gazit, S.

Effectiveness of Mask Wearing to Control Community Spread of SARS-CoV-2

Saige Blanchard — Mon, 03 Jan 2022 06:00:00 +0000

Date Added:

January 3, 2022

Journal/Publication:

Journal of the American Medical Association

Publisher:

American Medical Association

Publication Date:

February 10, 2021

Issue:

Volume:

325

Pages:

998-999

URL:

Effectiveness of Mask Wearing to Control Community Spread of SARS-CoV-2

Type:

Community-Based Research Results

Format:

Article

DOI (1):

10.1001/jama.2021.1505

Keywords

MeSH

A summary of what we know about the effectiveness of masks for preventing the spread of SARS COV2. James W. Mold, MD, MPH

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Prior to the coronavirus disease 2019 (COVID-19) pandemic, the efficacy of community mask wearing to reduce the spread of respiratory infections was controversial because there were no solid relevant data to support their use. During the pandemic, the scientific evidence has increased. Compelling data now demonstrate that community mask wearing is an effective nonpharmacologic intervention to reduce the spread of this infection, especially as source control to prevent spread from infected persons, but also as protection to reduce wearers’ exposure to infection.

Author/s:

Brooks, J. T., Butler, J. C.

Discriminating Multisystem Inflammatory Syndrome in Children Requiring Treatment from Common Febrile Conditions in Outpatient Settings

Devin Evans — Thu, 21 Jan 2021 06:00:00 +0000

Date Added:

January 21, 2021

Journal/Publication:

The Journal of Pediatrics

Publication Date:

October 13, 2020

Volume:

229

Pages:

26-32

URL:

Discriminating Multisystem Inflammatory Syndrome in Children Requiring Treatment from Common Febrile Conditions in Outpatient Settings

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1016/j.jpeds.2020.10.013

Keywords

kawasaki disease

SARS-CoV-2

multisystem inflammatory syndrome in children

myocarditis

COVID-19

coronavirus

PMID (1):

33065115

MeSH

pediatric multisystem inflammatory disease, COVID-19 related

SARS-CoV-2

child

C-Reactive Protein

Guidance regarding how to distinguish post-COVID multi-system inflammatory syndrome from other febrile illnesses in children. James W. Mold, MD, MPH

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Objectives: To examine whether patients with multisystem inflammatory syndrome in children (MIS-C) demonstrated well-defined clinical features distinct from other febrile outpatients, given the difficulties of seeing acute care visits during the severe acute respiratory syndrome coronavirus 2 pandemic and the risks associated with both over- and underdiagnosis of MIS-C.

Study design: This case-controlled study compared patients diagnosed with and treated for MIS-C at a large urban children's hospital with patients evaluated for fever at outpatient acute care visits during the peak period of MIS-C. Symptomatology and available objective data were extracted. Comparisons were performed using t tests with corrections for multiple comparisons, and multivariable logistic regression to obtain ORs.

Results: We identified 44 patients with MIS-C between April 16 and June 10, 2020. During the same period, 181 pediatric patients were evaluated for febrile illnesses in participating outpatient clinics. Patients with MIS-C reported greater median maximum reported temperature height (40°C vs 38.9, P < .0001), and increased frequency of abdominal pain (OR 12.5, 95% CI [1.65-33.24]), neck pain (536.5, [2.23-129,029]), conjunctivitis (31.3, [4.6-212.8]), oral mucosal irritation (11.8, [1.4-99.4]), extremity swelling or rash (99.9, [5-1960]), and generalized rash (7.42, [1.6-33.2]). Patients with MIS-C demonstrated lower absolute lymphocyte (P < .0001) and platelet counts (P < .05) and greater C-reactive protein concentrations (P < .001).

Conclusions: Patients treated for MIS-C due to concern for potential cardiac injury show combinations of features distinct from other febrile patients seen in outpatient clinics during the same period.

Author/s:

Carlin, Rebecca F., Fischer, Avital M., Pitlowsky, Zachary, Abel, Dori, Sewell, Taylor B., Landau, Erika G., Caddle, Steve, Robbins-Milne, Laura, Boneparth, Alexis, Milner, Josh D., Cheung, Eva W., Zachariah, Philp, Stockwell, Mellissa S., Anderson, Brett R., Gorelik, Mark

A national consensus management pathway for paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS): results of a national Delphi process

Devin Evans — Thu, 21 Jan 2021 06:00:00 +0000

Date Added:

January 21, 2021

Journal/Publication:

Lancet Child Adolescent Health

Publication Date:

September 18, 2020

Issue:

Volume:

Pages:

133-141

URL:

A national consensus management pathway for paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS): results of a national Delphi process

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1016/S2352-4642(20)30304-7

Keywords

PMID (1):

32956615

MeSH

pediatric multisystem inflammatory disease, COVID-19 related

COVID-19

child

Consensus recommendations for management of children with multi-system inflammatory syndrome following COVID-19. (The best we are likely to do because of difficulties conducting RCTs with children and small numbers of cases.) James W. Mold, MD, MPH

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Paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) is a novel condition that was first reported in April, 2020. We aimed to develop a national consensus management pathway for the UK to provide guidance for clinicians caring for children with PIMS-TS. A three-phase online Delphi process and virtual consensus meeting sought consensus over the investigation, management, and research priorities from multidisciplinary clinicians caring for children with PIMS-TS. We used 140 consensus statements to derive a consensus management pathway that describes the initial investigation of children with suspected PIMS-TS, including blood markers to help determine the severity of disease, an echocardiogram, and a viral and septic screen to exclude other infectious causes of illness. The importance of a multidisciplinary team in decision making for children with PIMS-TS is highlighted throughout the guidance, along with the recommended treatment options, including supportive care, intravenous immunoglobulin, methylprednisolone, and biological therapies. These include IL-1 antagonists (eg, anakinra), IL-6 receptor blockers (eg, tocilizumab), and anti-TNF agents (eg, infliximab) for children with Kawasaki disease-like phenotype and non-specific presentations. Use of a rapid online Delphi process has made it possible to generate a national consensus pathway in a timely and cost-efficient manner in the middle of a global pandemic. The consensus statements represent the views of UK clinicians and are applicable to children in the UK suspected of having PIMS-TS. Future evidence will inform updates to this guidance, which in the interim provides a solid framework to support clinicians caring for children with PIMS-TS. This process has directly informed new PIMS-TS specific treatment groups as part of the adaptive UK RECOVERY trial protocol, which is the first formal randomised controlled trial of therapies for PIMS-TS globally.

Author/s:

Harwood, Rachel, Allin, Benjamin, Jones, Christine E., Whittaker, Elizabeth, Ramnarayan, Padmanabhan, Ramanan, Athimalaipet V., Kaleem, Musa, Tulloh, Robert, Peters, Mark J., Almond, Sarah, Davis, Peter J., Levin, Michael, Tometzki, Andrew, Faust, Saul N., Knight, Marian, Kenny, Simon

The Advisory Committee on Immunization Practices’ Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine — United States, December 2020

Devin Evans — Thu, 21 Jan 2021 06:00:00 +0000

Date Added:

January 21, 2021

Journal/Publication:

Morbidity and Mortality Weekly Report

Publisher:

CDC

Publication Date:

December 18, 2020

Issue:

Volume:

Pages:

1922-1924

URL:

The Advisory Committee on Immunization Practices’ Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine — United States, December 2020

Type:

Public Health Announcements

Format:

Article

DOI (1):

10.15585/mmwr.mm6950e2

Keywords

immunizations

Pfizer–BioNTech mRNA vaccine

PMID (1):

33332292

MeSH

Summary and conclusions of the ACIP regarding the Pfizer COVID-19 vaccine based upon the RCT data available from Pfizer. James W. Mold, MD, MPH

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On December 11, 2020, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the Pfizer-BioNTech COVID-19 (BNT162b2) vaccine (Pfizer, Inc; Philadelphia, Pennsylvania), a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1). Vaccination with the Pfizer-BioNTech COVID-19 vaccine consists of 2 doses (30 μg, 0.3 mL each) administered intramuscularly, 3 weeks apart. On December 12, 2020, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation* for use of the Pfizer-BioNTech COVID-19 vaccine in persons aged ≥16 years for the prevention of COVID-19. To guide its deliberations regarding the vaccine, ACIP employed the Evidence to Recommendation (EtR) Framework,† using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.§ The recommendation for the Pfizer-BioNTech COVID-19 vaccine should be implemented in conjunction with ACIP's interim recommendation for allocating initial supplies of COVID-19 vaccines (2). The ACIP recommendation for the use of the Pfizer-BioNTech COVID-19 vaccine under EUA is interim and will be updated as additional information becomes available.

Author/s:

Oliver, Sara E., Gargano, Julia W., Marin, Mona, Wallace, Megan, Curran, Kathryn G., Chamberland, Mary, McClung, Nancy, Campos-Outcalt, Doug, Morgan, Rebecca L., Mbaeyi, Sarah, Romero, Jose R., Talbot, H.K., Lee, Grace M., Bell, Beth P., Dooling, Kathleen

Maintaining Safety with SARS-CoV-2 Vaccines

Devin Evans — Thu, 14 Jan 2021 06:00:00 +0000

Date Added:

January 14, 2021

Journal/Publication:

The New England Journal of Medicine

Publication Date:

December 30, 2020

URL:

Maintaining Safety with SARS-CoV-2 Vaccines

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1056/NEJMra2035343

Keywords

Pfizer–BioNTech mRNA vaccine

Pfizer

PMID (1):

33378605

MeSH

SARS-CoV-2

vaccination

COVID-19 Vaccines

Adverse Drug Reaction Reporting Systems

COVID-19

Experience with and recommendations for management of adverse reactions to the SARS-2 (COVID-19) mRNA vaccines. James W. Mold, MD, MPH

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To date, the development of mRNA vaccines for the prevention of infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a success story, with no serious concerns identified in the ongoing phase 3 clinical trials.1 Minor local side effects such as pain, redness, and swelling have been observed more frequently with the vaccines than with placebo. Systemic symptoms such as fever, fatigue, headache, and muscle and joint pain have also been somewhat more common with the vaccines than with placebo, and most have occurred during the first 24 to 48 hours after vaccination.1 In the phase 1–3 clinical trials of the Pfizer–BioNTech and Moderna mRNA vaccines, potential participants with a history of an allergic reaction to any component of the vaccine were excluded. The Pfizer–BioNTech studies also excluded participants with a history of severe allergy associated with any vaccine (see the protocols of the two trials, available with the full text of the articles at NEJM.org, for full exclusion criteria).1,2 Hypersensitivity adverse events were equally represented in the placebo (normal saline) and vaccine groups in both trials.1

Author/s:

Castells, Mariana C., Phillips, Elizabeth J.

REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19

Devin Evans — Thu, 14 Jan 2021 06:00:00 +0000

Date Added:

January 14, 2021

Journal/Publication:

The New England Journal of Medicine

Publication Date:

December 17, 2020

URL:

REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1056/NEJMoa2035002

Keywords

PMID (1):

33332778

MeSH

A review of what is currently known about the monoclonal antibody cocktail for outpatient treatment of COVID-19. James W. Mold, MD, MPH

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Background: Recent data suggest that complications and death from coronavirus disease 2019 (Covid-19) may be related to high viral loads.

Methods: In this ongoing, double-blind, phase 1-3 trial involving nonhospitalized patients with Covid-19, we investigated two fully human, neutralizing monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, used in a combined cocktail (REGN-COV2) to reduce the risk of the emergence of treatment-resistant mutant virus. Patients were randomly assigned (1:1:1) to receive placebo, 2.4 g of REGN-COV2, or 8.0 g of REGN-COV2 and were prospectively characterized at baseline for endogenous immune response against SARS-CoV-2 (serum antibody-positive or serum antibody-negative). Key end points included the time-weighted average change from baseline in viral load from day 1 through day 7 and the percentage of patients with at least one Covid-19-related medically attended visit through day 29. Safety was assessed in all patients.

Results: Data from 275 patients are reported. The least-squares mean difference (combined REGN-COV2 dose groups vs. placebo group) in the time-weighted average change in viral load from day 1 through day 7 was -0.56 log10 copies per milliliter (95% confidence interval [CI], -1.02 to -0.11) among patients who were serum antibody-negative at baseline and -0.41 log10 copies per milliliter (95% CI, -0.71 to -0.10) in the overall trial population. In the overall trial population, 6% of the patients in the placebo group and 3% of the patients in the combined REGN-COV2 dose groups reported at least one medically attended visit; among patients who were serum antibody-negative at baseline, the corresponding percentages were 15% and 6% (difference, -9 percentage points; 95% CI, -29 to 11). The percentages of patients with hypersensitivity reactions, infusion-related reactions, and other adverse events were similar in the combined REGN-COV2 dose groups and the placebo group.

Conclusions: In this interim analysis, the REGN-COV2 antibody cocktail reduced viral load, with a greater effect in patients whose immune response had not yet been initiated or who had a high viral load at baseline. Safety outcomes were similar in the combined REGN-COV2 dose groups and the placebo group.

Author/s:

Weinreich, David M., Sivapalasingam, Sumathi, Norton, THomas,, Ali, Shazia, Gao, Haitao, Bhore, Rafia, Musser, Bret J., Soo, Yuhwen, Rofail, Diana, Im, Joseph, Perry, Christina, Pan, Cynthia, Hosain, Romana, Mahmood, Adnan, Davis, John D., Turner, Kenneth C., Hooper, Andrea T., Hamilton, Jennifer D., Baum, Alina, Kyratsous, Christos A., Kim, Yunji, Cook, Amanda, Kampman, Wendy, Kohli, Anita, Sachdeva. Yessica, Graber, Ximena, Kowal, Bari, DiCioccio, Thomas, Stahl, Neil, Lipsich, Leah, Braunstein, Ned, Herman, Gary, Yancopoulos, George D.

Masks and Face Coverings for the Lay Public : A Narrative Update

Devin Evans — Thu, 14 Jan 2021 06:00:00 +0000

Date Added:

January 14, 2021

Journal/Publication:

Annals of Internal Medicine

Publication Date:

December 29, 2020

URL:

Masks and Face Coverings for the Lay Public : A Narrative Update

Type:

Meta-analyses, Reviews, and Guidelines, Patient Education Materials

Format:

Article

DOI (1):

10.7326/M20-6625

Keywords

PMID (1):

33370173

MeSH

Policy

Respiratory Physiological Phenomena

A narrative summary of our current understandings regarding mask wearing and prevention of the spread of COVID-19. James W. Mold, MD, MPH

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Whether and when to mandate the wearing of facemasks in the community to prevent the spread of coronavirus disease 2019 remains controversial. Published literature across disciplines about the role of masks in mitigating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is summarized. Growing evidence that SARS-CoV-2 is airborne indicates that infection control interventions must go beyond contact and droplet measures (such as handwashing and cleaning surfaces) and attend to masking and ventilation. Observational evidence suggests that masks work mainly by source control (preventing infected persons from transmitting the virus to others), but laboratory studies of mask filtration properties suggest that they could also provide some protection to wearers (protective effect). Even small reductions in individual transmission could lead to substantial reductions in population spread. To date, only 1 randomized controlled trial has examined a community mask recommendation. This trial did not identify a significant protective effect and was not designed to evaluate source control. Filtration properties and comfort vary widely across mask types. Masks may cause discomfort and communication difficulties. However, there is no evidence that masks result in significant physiologic decompensation or that risk compensation and fomite transmission are associated with mask wearing. The psychological effects of masks are culturally shaped; they may include threats to autonomy, social relatedness, and competence. Evidence suggests that the potential benefits of wearing masks likely outweigh the potential harms when SARS-CoV-2 is spreading in a community. However, mask mandates involve a tradeoff with personal freedom, so such policies should be pursued only if the threat is substantial and mitigation of spread cannot be achieved through other means.

Author/s:

Czypionka, Thomas, Greenhalgh, Trisha, Bassler, Dirk, Bryant, Manuel B.

SARS-CoV-2 immunity: review and applications to phase 3 vaccine candidates

Devin Evans — Fri, 13 Nov 2020 06:00:00 +0000

Date Added:

November 13, 2020

Journal/Publication:

Lancet

Publication Date:

October 13, 2020

Issue:

10262

Volume:

396

Pages:

1595-1606

URL:

SARS-CoV-2 immunity: review and applications to phase 3 vaccine candidates

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1016/S0140-6736(20)32137-1

Keywords

PMID (1):

33065034

MeSH

Anitbodies, Monoclonal

A review of what is currently known about the immune response to COVID-19 and its implications for therapy and vaccines. James W. Mold, MD, MPH

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Understanding immune responses to severe acute respiratory syndrome coronavirus 2 is crucial to understanding disease pathogenesis and the usefulness of bridge therapies, such as hyperimmune globulin and convalescent human plasma, and to developing vaccines, antivirals, and monoclonal antibodies. A mere 11 months ago, the canvas we call COVID-19 was blank. Scientists around the world have worked collaboratively to fill in this blank canvas. In this Review, we discuss what is currently known about human humoral and cellular immune responses to severe acute respiratory syndrome coronavirus 2 and relate this knowledge to the COVID-19 vaccines currently in phase 3 clinical trials.

Author/s:

Gregory A., Ovsyannikova , Inna G., Kennedy, Richard B.