SARS-CoV-2

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

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

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.

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

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

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.

Maintaining Safety with SARS-CoV-2 Vaccines

Author/s: 
Castells, Mariana C., Phillips, Elizabeth J.

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

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

Author/s: 
Czypionka, Thomas, Greenhalgh, Trisha, Bassler, Dirk, Bryant, Manuel B.

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.

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

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.

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. 

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