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Outbreaks, Alerts and Hot Topics

March 2022

Updated CDC Guidance on the COVID-19 Vaccine Primary Series and Masking in Public


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Column Editor: Angela Myers, MD, MPH | Director, Division of Infectious Diseases | Professor of Pediatrics, UMKC School of Medicine | Medical Editor, The Link Newsletter


In the last full week of February, the Centers for Disease Control and Prevention (CDC) updated its guidance for timing of the COVID-19 vaccine primary series administration and masking in public. Since there are so many nuances to the COVID-19 recommendations, perhaps this guidance warrants a summary.

First, the updated CDC guidance for the mRNA vaccines recommends that the second vaccine dose be given up to eight weeks after the first vaccine dose. These recommendations are primarily for people 12-39 years and especially males. The previous recommendations of three weeks for Pfizer’s vaccine (BNT162b2) and four weeks for Moderna’s vaccine (mRNA-1273) remain in place for all those ≥65 years of age, immune suppressed, and those in whom faster protection may be needed due to high risk of severe disease.

What prompted this change? Vaccine Adverse Event Reporting System (VAERS) data has shown that the risk of myocarditis (mostly after vaccine dose #2) is 40 per million males aged 18-24 years. Additional data from the United States Vaccine Safety Datalink, Canada, the U.K., France and Germany has shown that the risk of myocarditis with Moderna vaccine is approximately 1.5 to eight times higher compared to Pfizer.1,2 At the Feb. 4 meeting of the Advisory Committee on Immunization Practices (ACIP), data from a retrospective passive surveillance cohort study in Canada compared various timing between first and second doses of vaccine with different combinations of Moderna (mRNA-1273) and Pfizer (BNT162b2) in adults 18-24 years. This study examined intervals that were less than four weeks, five to seven weeks, and eight weeks or more. Every vaccine combination included in the study (Pfizer-Pfizer, Pfizer-Moderna, Moderna-Moderna) showed a reduced risk of myocarditis as the time interval lengthened between dose 1 and 2, with the largest reduction noted at eight weeks or more.3 (Table 1) Of note, the Moderna-Pfizer combination was not included in the study due to a low number of recipients of this combination and no reported cases of myocarditis.

Additional data from two Canadian provinces (Quebec and British Columbia) in adults aged ≥18 years found that vaccine efficacy was improved with a seven-week or more interval compared to a three- to four-week interval between dose 1 and 2 from 79%-85% and 87%-93% to 89%-91% and 94%-97% against infection and hospitalization, respectively.4 Similar data of increased vaccine efficacy with an extended interval (three to four weeks vs. six to 14 weeks) was found in an observational cohort study in the U.K. as well. This data has prompted many countries including Canada, the U.K., Sweden, Norway, Finland, Denmark, Singapore, Taiwan, France and Germany to preferentially recommend Pfizer vaccine for younger age groups (<30 years) and extended intervals ranging from six to 12 weeks. The limitations to this data include that it was collected in the summer and fall 2021 prior to the Omicron variant, case definitions vary across countries, and national vaccine policies have changed over time, which influences which vaccine people receive and the timing of doses. That said, the rare but serious side effect of myocarditis was reduced, and neutralizing antibody titers were higher. Vaccine effectiveness improved between 5% and 10% by increasing the interval between doses. This situation appears to be a win-win.

Masking recommendations have changed throughout the pandemic as scientific data has shown the benefits of mask wearing and as the virus itself has evolved over the last two-plus years. Thus, it makes sense that guidance about mask wearing would periodically be updated as well. On Feb. 25, the CDC published new recommendations in the form of a green, yellow and red stoplight to decide who and when people should be masked.5 (Table 2) This link will take you to the webpage where you can view a map of the U.S. and look up your specific county: Currently, no state has uniform transmission rates. Some states have a little more red or a little more yellow and green, but all states have two to three different levels of transmission across counties. In counties that are in the low category, it is now recommended only that people wear a mask based on their level of risk and personal preference, with the exception of public transportation for which mask wearing is still recommended. In the medium category, it is recommended that people at high risk for severe disease continue to mask inside public places and consider higher grade masks, such as respirators. Additionally, it is recommended that healthy people around high-risk individuals consider testing prior to social contact and wear a mask when indoors. Finally, in the high transmission setting, it is recommended that everyone wear a well-fitted mask in all settings (including schools) when indoors and that high-risk individuals wear a mask that provides the most protection. To me, this represents a sign that we are possibly seeing a light at the end of this very long tunnel and that soon we will be able to see each other’s whole faces in most, if not all, public settings.


Table 1. Rates of myocarditis following a two-dose vaccine series with varied product combinations and interval between doses

Vaccine product and schedule Rate of myocarditis per million doses
 Pfizer-Pfizer <30 days 94.5
 Pfizer-Pfizer 31-55 days 64.4
 Pfizer-Pfizer ≥56 days 11.1
 Moderna-Moderna <30 days 376.5
 Moderna-Moderna 31-55 days 331.4
 Moderna-Moderna ≥56 days 132.5
 Pfizer-Moderna <30 days 777.2
 Pfizer-Moderna 31-55 days 318.9
 Pfizer-Moderna ≥56 days 194.1


Table 2. Definitions of high, medium and low COVID-19 community transmission

New COVID-19 cases per 100,000 people within 7 days Indicators Low Medium High
  • Admissions per 100,000 population
  • Percent of inpatient beds with COVID-19 patients
  • <10
  • <10%
  • 10-19.9
  • 10-14.9%
  • ≥20
  • ≥15%
  • Admissions per 100,000 population
  • Percent of inpatient beds with COVID-19 patients
  • <10
  • <10%
  • >10
  • ≥10%
  • Consider a mask if high-risk or personal preference
  • Mask while using public transportation
  • Mask if you are high-risk and consider respirator
  • Mask if you are around a person at high-risk
  • Everyone should mask and high-risk should wear a mask that provides the most protection


References: (All references accessed February 27, 2022)