New coronavirus subvariants escape antibodies from vaccination and prior Omicron infection, studies suggest

Authors: Jacqueline Howard, CNN June 23, 2022

Omicron subvariants BA.4 and BA.5 appear to escape antibody responses among both people who had previous Covid-19 infection and those who have been fully vaccinated and boosted, according to new data from researchers at Beth Israel Deaconess Medical Center, of Harvard Medical School.

However, Covid-19 vaccination is still expected to provide substantial protection against severe disease, and vaccine makers are working on updated shots that might elicit a stronger immune response against the variants.

The levels of neutralizing antibodies that a previous infection or vaccinations elicit are several times lower against the BA.4 and BA.5 subvariants compared with the original coronavirus, according to the new research published in the New England Journal of Medicine on Wednesday.

“We observed 3-fold reductions of neutralizing antibody titers induced by vaccination and infection against BA4 and BA5 compared with BA1 and BA2, which are already substantially lower than the original COVID-19 variants,” Dr. Dan Barouch, an author of the paper and director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston, wrote in an email to CNN.

“Our data suggest that these new Omicron subvariants will likely be able to lead to surges of infections in populations with high levels of vaccine immunity as well as natural BA1 and BA2 immunity,” Barouch wrote. “However, it is likely that vaccine immunity will still provide substantial protection against severe disease with BA4 and BA5.”

The newly published findings echo separate research by scientists at Columbia University.

They recently found that the BA.4 and BA.5 viruses were more likely to escape antibodies from the blood of fully vaccinated and boosted adults compared with other Omicron subvariants, raising the risk of vaccine-breakthrough Covid-19 infections.

The authors of that separate study say their results point to a higher risk for reinfection, even in people who have some prior immunity against the virus. The US Centers for Disease Control and Prevention estimates 94.7% of the US population ages 16 and older have antibodies against the coronavirus that causes Covid-19 through vaccination, infection, or both.

BA.4 and BA.5 caused an estimated 35% of new Covid-19 infections in the United States last week, up from 29% the week before, according to data shared by the US Centers for Disease Control and Prevention on Tuesday.

BA.4 and BA.5 are the fastest spreading variants reported to date, and they are expected to dominate Covid-19 transmission in the United States, United Kingdom and the rest of Europe within the next few weeks, according to the European Centre for Disease Prevention and Control.

‘COVID-19 still has the capacity to mutate further’

In the New England Journal of Medicine paper, among 27 research participants who had been vaccinated and boosted with the Pfizer/BioNTech coronavirus vaccine, the researchers found that two weeks after the booster dose, levels of neutralizing antibodies against Omicron subvariants were much lower than the response against the original coronavirus.

The neutralizing antibody levels were lower by a factor of 6.4 against BA.1; by a factor of 7 against BA.2; by a factor of 14.1 against BA.2.12.1 and by a factor of 21 against BA.4 or BA.5, the researchers described.

Among 27 participants who had previously been infected with the BA.1 or BA.2 subvariants a median of 29 days earlier, the researchers found similar results.

In those with previous infection – most of whom also had been vaccinated – the researchers described neutralizing antibody levels that were lower by a factor of 6.4 against BA.1; by a factor of 5.8 against BA.2; by a factor of 9.6 against BA.2.12.1 and by a factor of 18.7 against BA.4 or BA.5.

More research is needed to determine what exactly the neutralizing antibody levels mean for vaccine effectiveness and whether similar findings would emerge among a larger group of participants.

“Our data suggest that COVID-19 still has the capacity to mutate further, resulting in increased transmissibility and increased antibody escape,” Barouch wrote in the email. “As pandemic restrictions are lifted, it is important that we remain vigilant and keep studying new variants and subvariants as they emerge.”

A separate study, published in the journal Nature last week, found that Omicron may evolve mutations to evade the immunity elicited by having a previous BA.1 infection, which suggests that vaccine boosters based on BA.1 may not achieve broad-spectrum protection against new Omicron subvariants like BA.4 and BA.5.

As for what all this means in the real world, Dr. Wesley Long, an experimental pathologist at Houston Methodist Hospital, told CNN that people should be aware that they could get sick again, even if they’ve had Covid-19 before.

“I think I’m a little bit worried about people who’ve had it maybe recently having a false sense of security with BA.4 and BA.5 on the increase, because we have seen some cases of reinfection and I have seen some cases of reinfection with people who had a BA.2 variant in the last few months,” he said.

Some vaccine makers have been developing variant-specific vaccines to improve the antibody responses against coronavirus variants and subvariants of concern.

“Reinfections are going to be pretty inevitable until we have vaccines or widespread mandates that are going to prevent cases rising again. But the good news is that we are in, I think, a much better spot than we were without the vaccines,” said Pavitra Roychoudhury, an acting instructor at the University of Washington’s Department of Laboratory Medicine and Pathology, who was not involved in the New England Journal of Medicine paper.

“There’s so much of this virus out there that it seems inevitable,” she said about Covid-19 infections. “Hopefully the protections that we have in place are going to lead to mostly mild infection.”

Efforts underway to update Covid-19 vaccines

Moderna’s bivalent Covid-19 vaccine booster, named mRNA-1273.214, elicited a “potent” immune responses against the Omicron subvariants BA.4 and BA.5, the company said Wednesday.

This bivalent booster vaccine candidate contains components of both Moderna’s original Covid-19 vaccine and a vaccine that targets the Omicron variant. The company said it is working to complete regulatory submissions in the coming weeks requesting to update the composition of its booster vaccine to be mRNA-1273.214.

“In the face of SARS-CoV-2’s continued evolution, we are very encouraged that mRNA-1273.214, our lead booster candidate for the fall, has shown high neutralizing titers against the BA.4 and BA.5 subvariants, which represent an emergent threat to global public health,” Stéphane Bancel, chief executive officer of Moderna, said in Wednesday’s announcement. SARS-CoV-2 is the coronavirus that causes Covid-19.

“We will submit these data to regulators urgently and are preparing to supply our next generation bivalent booster starting in August, ahead of a potential rise in SARS-CoV-2 infections due to Omicron subvariants in the early fall,” Bancel said.

The US Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee is meeting next week to discuss the composition of Covid-19 vaccines that could be used as boosters this fall.

The data that Moderna released Wednesday, which has not been published in a peer-reviewed journal, showed that one month after a 50-microgram dose of the mRNA-1273.214 vaccine was administered in people who had been vaccinated and boosted, the vaccine elicited “potent” neutralizing antibody responses against BA.4 and BA.5, boosting levels 5.4-fold in all participants regardless of whether they had a prior Covid-19 infection and by 6.3-fold in the subset of those with no history of prior infection. These levels of neutralizing antibodies were about 3-fold lower than previously reported neutralizing levels against BA.1, Moderna said.

These findings add to the data that Moderna previously released earlier this month, showing that the 50-microgram dose of the bivalent booster generated a stronger antibody response against Omicron than the original Moderna vaccine.


Sign up here to get The Results Are In with Dr. Sanjay Gupta every Tuesday from the CNN Health team.

Moderna’s data suggest that “the bivalent booster might confer greater protection against the BA.4 and BA.5 omicron strains than readministering the original vaccine to increase protection across the population. Although the information is based on antibody levels, the companies comment that similar levels of antibody protected against clinical illness caused by other strains is the first suggestion of an emerging ‘immune correlate’ of protection, although it is hoped that this ongoing study is also assessing rates of clinical illness as well as antibody responses,” Penny Ward, an independent pharmaceutical physician and visiting professor in pharmaceutical medicine at King’s College London, said in a statement released by the UK-based Science Media Centre on Wednesday. She was not involved in Moderna’s work.

“It has been reported previously that the bivalent vaccine is well tolerated with temporary ‘reactogenic’ effects similar to those following the univalent booster injection so we can anticipate that this new mixed vaccine should be well tolerated,” Ward said in part. “As we head towards the autumn with omicron variants dominating the covid infection landscape, it certainly makes sense to consider use of this new bivalent vaccine, if available.”

Association of COVID-19 Vaccination During Pregnancy With Incidence of SARS-CoV-2 Infection in Infants

Authors: Ellen Øen Carlsen, MD1Maria C. Magnus, PhD1Laura Oakley, PhD1,2et alDeshayne B. Fell, PhD3,4Margrethe Greve-Isdahl, MD5Jonas Minet Kinge, PhD1,6Siri E. Håberg, MD, PhD

JAMA Intern Med. Published online June 1, 2022. doi:10.1001/jamainternmed.2022.2442

Key Points

Question  Is maternal COVID-19 vaccination during the second or third trimester of pregnancy associated with reduced risk of COVID-19 within the first 4 months of life in their infants?

Findings  In this register-based cohort study of all live-born infants in Norway, there was a lower incidence of a positive SARS-CoV-2 test result in infants born to women vaccinated with a messenger RNA vaccine during pregnancy. The risk was lower during the period dominated by the Delta variant than during the Omicron-dominated period.

Meaning  The study results suggest that maternal COVID-19 vaccination during pregnancy could protect against infant SARS-CoV-2 infection in the early months of life.


Importance  Pregnant women are recommended to receive COVID-19 vaccination to reduce risk of severe COVID-19. Whether vaccination during pregnancy also provides passive protection to infants after birth remains unclear.

Objective  To determine whether COVID-19 vaccination in pregnancy was associated with reduced risk of COVID-19 in infants up to age 4 months during COVID-19 pandemic periods dominated by Delta and Omicron variants.

Design, Setting, and Participants  This nationwide, register-based cohort study included all live-born infants born in Norway between September 1, 2021, and February 28, 2022.

Exposures  Maternal messenger RNA COVID-19 vaccination during second or third trimester compared with no vaccination before or during pregnancy.

Main Outcomes and Measures  The risk of a positive polymerase chain reaction test result for SARS-CoV-2 during an infant’s first 4 months of life by maternal vaccination status during pregnancy with either dose 2 or 3 was estimated, as stratified by periods dominated by the Delta variant (between September 1 and December 31, 2021) or Omicron variant (after January 1, 2022, to the end of follow-up on April 4, 2022). A Cox proportional hazard regression was used, adjusting for maternal age, parity, education, maternal country of birth, and county of residence.

Results  Of 21 643 live-born infants, 9739 (45.0%) were born to women who received a second or third dose of a COVID-19 vaccine during pregnancy. The first 4 months of life incidence rate of a positive test for SARS-CoV-2 was 5.8 per 10 000 follow-up days. Infants of mothers vaccinated during pregnancy had a lower risk of a positive test compared with infants of unvaccinated mothers and lower risk during the Delta variant–dominated period (incidence rate, 1.2 vs 3.0 per 10 000 follow-up days; adjusted hazard ratio, 0.29; 95% CI, 0.19-0.46) compared with the Omicron period (incidence rate, 7.0 vs 10.9 per 10 000 follow-up days; adjusted hazard ratio, 0.67; 95% CI, 0.57-0.79).

Conclusions and Relevance  The results of this Norwegian population-based cohort study suggested a lower risk of a positive test for SARS-CoV-2 during the first 4 months of life among infants born to mothers who were vaccinated during pregnancy. Maternal COVID-19 vaccination may provide passive protection to young infants, for whom COVID-19 vaccines are currently not available.


The risk of critical illness because of COVID-19 has been reported to be higher in infants younger than 1 year compared with older children.1 To our knowledge, no COVID-19 vaccines are currently available for infants or children younger than 5 years. Transplacental transfer of maternal vaccine-derived antibodies against pertussis and seasonal influenza has been demonstrated following vaccination during pregnancy, and maternal immunization provides passive protection against infection to infants during the first months after birth.2,3 It is plausible that COVID-19 vaccination during pregnancy could provide passive protection from COVID-19 to infants during their first months of life.4 Vaccine-derived maternal antibodies have been identified in cord blood after COVID-19 vaccination during pregnancy, and a recent study found maternal vaccination to be associated with a 61% reduced risk of infant hospitalization for COVID-19.57 This study evaluated the association between maternal COVID-19 vaccination during pregnancy and incidence of infant SARS-CoV-2 infection during the first 4 months of life, as well as whether the association differed according to Delta variant and Omicron variant–dominated time periods.811


Study Population and Data Sources

All live births in Norway between September 1, 2021, and February 28, 2022, were identified in the Medical Birth Registry of Norway (Figure 1),12 which captures all pregnancies ending after completion of gestational week 12. Newborns were excluded if the mother or infant did not have a permanent national identification number, which was used to link information across registries.

All data used in this study were provided by the Emergency Preparedness Register for COVID-19 (Beredt C19),13 which is run by the Norwegian Institute of Public Health. This register was established in response to the COVID-19 pandemic in 2020 in accordance with the Health Preparedness Act §2-4 and contains daily updated data from the Norwegian health registries.

COVID-19 Vaccination During Pregnancy

The Norwegian Immunization Register14 contains registrations of all COVID-19 vaccinations, including dates of all doses and the type of vaccine product. Vaccine doses reported fewer than 20 days after the previous dose were not included. Women who received a second or third dose of a messenger RNA (mRNA) vaccine after gestational day 83 and up to 14 days before delivery were considered vaccinated. Infants born to women who received their third or fourth vaccine dose between 13 and 7 days before birth were excluded, as they would be censored before birth in the statistical analyses. We excluded infants born to women vaccinated outside Norway while pregnant and those vaccinated exclusively before pregnancy or who only received dose 1 during pregnancy because the maternal antibody level and possible transplacental transfer of antibodies for these scenarios are uncertain.1517

SARS-CoV-2 Infection

During the study period (September 1, 2021, to April 4, 2022), the date of testing and results of all SARS-CoV-2 polymerase chain reaction (PCR) tests were registered in the Norwegian Surveillance System for Communicable Diseases.18 We included the first positive PCR test for SARS-CoV-2 registered at least 1 day after birth and within 122 days after birth (4 months of age). Similarly, we identified women with a positive SARS-CoV-2 test 14 days or more before giving birth. In Norway, PCR tests were free of charge and widely available.


From the Medical Birth Registry of Norway, we derived maternal age at conception (<24, 25-29, 30-34, 35-39, ≥40 years) and extracted information on parity (0, 1, or ≥2) and calendar week of birth. The registered gestational age in the birth registry was estimated from routine ultrasonography assessments or last menstrual period if there were no ultrasonography estimates. From the Population Registry of Norway, we obtained information on maternal country of birth (Scandinavian country [Norway, Denmark, and Sweden], or non-Scandinavian countries) and current county of residence (Oslo, Viken, or other Norwegian county). From Statistics Norway we obtained information on the highest maternal educational level as of 2019 (no higher education, higher education ≤4 years, >4 years of higher education, or missing).

Statistical Analysis

We calculated incidence rates of SARS-CoV-2 infection (number of infants with positive tests among all infants at risk at the day of testing) in infants within 4 months after birth by maternal vaccination status. We split the follow-up time on December 31, 2021, by introducing a variable with 2 categories that corresponded to the time before this date (proxy for the Delta-dominated period) and after this date (proxy for the Omicron-dominated period). Using a Cox proportional hazards model, we estimated hazard ratios (HRs) for infant SARS-CoV-2 infection using calendar time (in days) as the time axis. Infant follow-up began on the date of birth. Observations were censored at age 4 months, death or emigration, date of when a woman received a vaccine dose outside Norway, or on April 4, 2022, whichever came first. For women vaccinated at the end of pregnancy or after pregnancy, infants were censored 14 days after the vaccination date of dose 1 and 7 days after dose 3 or 4. This was done because maternal vaccination within the last 14 days of pregnancy could potentially provide an exclusive protective effect from antibody transfer through breastfeeding or cocooning (ie, immunizing primary caretakers).19,20

We assessed differences in the Delta and Omicron periods by using linear combinations of the coefficients for vaccination status and an interaction term between vaccination status and period. Multivariable analyses adjusted for maternal age at conception, parity, educational level, county of residence, and maternal country of birth.

Sensitivity Analyses

First, we excluded infants born to women who had a positive SARS-CoV-2 test more than 14 days before delivery, as women with a history of COVID-19 might be less likely to become vaccinated during pregnancy and could transfer anti–SARS-CoV-2 antibodies across the placenta.5 Second, in separate analyses, we restricted the sample to (1) term-born infants, (2) infants who had the opportunity to reach 42 completed gestational weeks by the end of the inclusion period to avoid oversampling preterm births, (3) infants born to Scandinavian-born women, (4) infants born to first-time mothers, and (5) infants born to women who only received mRNA vaccines for all doses. Third, to obtain more robust results for the Omicron-dominated period, we used an alternative follow-up period starting on January 15, 2022, as after this date the circulating virus was more certain to be Omicron. Finally, as testing and risk of infection may differ by infant age, we used infant age in days as the time axis, while adjusting for week of birth.

Secondary Analyses

Using the Norwegian Patient Registry,21 we explored the risk of infant hospitalization for COVID-19. All hospital admissions were registered with admission and discharge dates, as well as diagnostic codes, using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10). We identified all infants with a hospitalization with the ICD-10 code U07.1 (COVID-19, virus identified) as the main diagnosis within the first 4 months of life and reported the crude proportions by maternal vaccination status.

To assess associations between maternal vaccination, even if not fully vaccinated, and incidence of a positive PCR test for SARS-CoV-2 among infants, we conducted a secondary analysis in which we compared the risk of a positive SARS-CoV-2 test in infants born to unvaccinated women with those with mothers who had received a first dose of an mRNA vaccine during the second or third trimester (these were excluded from the main analysis). Infants were censored 14 days after a woman received the second dose postpartum or during the last 14 days of pregnancy and 14 days after the first dose among the unvaccinated group. We compared the timing of vaccination in pregnancy in those who received only 1 dose in pregnancy with those who were fully vaccinated. Furthermore, we conducted a secondary analysis stratifying on whether the woman received COVID-19 vaccine dose number 2 or 3 during pregnancy.

To explore possible differences in the likelihood of being tested in infants among vaccinated and unvaccinated mothers, we assessed the proportions in each group that had at least 1 registered SARS-CoV-2 PCR test (positive or negative) before age 4 months. We calculated crude incidence rates for registration of a PCR test by maternal vaccination status. Again, infants were censored at time of death, emigration, or maternal receipt of a vaccine dose outside Norway. All analyses were conducted using Stata, version 16.0 SE (StataCorp).


Of 21 643 newborns included in the study, 9739 (45%) were born to women who received a second or third dose of a COVID-19 mRNA vaccine during the last 2 trimesters of pregnancy (Table 1). Fewer than 5 women received a fourth dose in pregnancy. Compared with vaccinated mothers, unvaccinated mothers were younger, had higher parity and lower education, and fewer were born in Scandinavia. The proportion of infants born to a vaccinated mother increased during the study period (eFigure 1A in the Supplement). Most newborns with a positive SARS-CoV-2 test during the fall of 2021 were born to unvaccinated mothers (eFigure 1B in the Supplement), but an infant’s age at the time of a positive test was similar between the groups (eFigure 1C in the Supplement). The number of tested infants decreased by mid-February 2022 (eFigure 1D in the Supplement).

Incidence of SARS-CoV-2 in Infants

A total of 906 infants (4.1%) were registered with a positive PCR test for SARS-CoV-2 during the first 4 months of life. Infants born to vaccinated mothers had a lower incidence of SARS-CoV-2 (Figure 2). During the Delta-dominated period (before January 1, 2022), crude incidence rates for a positive test were 1.2 per 10 000 follow-up days among infants born to vaccinated mothers and 3.0 per 10 000 follow-up days among infants born to unvaccinated mothers. The corresponding adjusted HR (aHR) for the Delta-dominated period was 0.29 (95% CI, 0.19-0.44) (Table 2). During the Omicron-dominated period (starting on January 1, 2022), the crude incidence rates for a positive SARS-CoV-2 test were 7.0 per 10 000 follow-up days among infants born to vaccinated mothers and 10.9 per 10 000 follow-up days among infants born to unvaccinated mothers (aHR, 0.67; 95% CI, 0.57-0.79) (Table 2). We observed no violation of the proportional hazard assumption.

Sensitivity Analyses

Results were robust in sensitivity analyses, although estimates were attenuated when restricting to infants born to Scandinavian-born women (eTables 1-6 in the Supplement). The results for the Omicron-dominated period when restricted to January 15 and later were similar to the main analyses (eTable 7 in the Supplement). Using the infant age as the time scale attenuated the association slightly (eTable 8 and eFigure 2 in the Supplement).

Secondary Analyses

The proportion of infants hospitalized with COVID-19 as the main diagnosis before age 4 months or April 4, 2022, was 0.07% in both groups. The numbers were too low to perform formal comparative analyses by maternal vaccination status (Table 1).

In addition to the 21 463 infants in the main analysis, 2839 infants were born to women who only received 1 dose of an mRNA vaccine during the second or third trimester of pregnancy and at least 14 days before delivery. The timing of vaccine doses was differentially distributed by calendar time and time interval before birth between those who received only 1 vs a second or third dose in pregnancy (eFigures 3 and 4 in the Supplement), and the mean follow-up time was shorter. Among those born to women who received 1 dose of vaccine, 36 infants had a positive SARS-CoV-2 PCR test, including fewer than 5 during the Delta-dominated period. The aHR for a positive test in infants during the Omicron-dominated period born to women with 1 dose of vaccine compared with infants born to unvaccinated women was 0.72 (95% CI, 0.50-1.03) (eTable 9 in the Supplement).

Among 824 infants born to women who received their third vaccine dose during pregnancy, none had a positive SARS-CoV-2 test during the Delta-dominated period. The risk of a positive test was lower for the Omicron-dominated period for those with a third dose (aHR, 0.22; 95% CI, 0.12-0.43) compared with those with a second dose (aHR, 0.70; 95% CI, 0.59-0.83) (eTable 10 in the Supplement).

The proportion of infants who had at least 1 PCR test for SARS-CoV-2 during follow-up differed by maternal vaccination status: 2309 infants (19.4%) born to unvaccinated mothers and 1206 infants (12.4%) born to vaccinated mothers (Table 1). Corresponding incidence rates were 19.7 per 10 000 follow-up days among infants born to unvaccinated women and 15.1 per 10 000 follow-up days among infants born to vaccinated women.


This cohort study of all live births in Norway between September 1, 2021, and February 28, 2022, found that COVID-19 vaccination during pregnancy was associated with a reduced risk of an infant receiving a positive PCR test for SARS-CoV-2 during the first 4 months of life. This association was present during periods dominated by the Delta and Omicron variants, although it was stronger in the former. Results were robust in sensitivity analyses, although the number of cases during the Delta-dominated period was low in some of the subgroups. The association was somewhat attenuated when restricted to infants born to Scandinavian-born women.

It is not unexpected that maternal COVID-19 vaccination during pregnancy could reduce infant risk of COVID-19, as similar protective benefits against infant infection have been documented for pertussis and influenza vaccination during pregnancy in randomized clinical trials and observational studies.2,3 Because the newborn’s immune system is naive, with limited antibody response during the first months of life, an important protection against infection comes from maternally transferred antibodies.2,3 Infants are at higher risk of severe COVID-19 compared with older children.1 As to our knowledge no COVID-19 vaccines are licensed for use in children younger than 5 years, an added benefit of maternal vaccination during pregnancy could be a protection of infants against SARS-CoV-2 infection during the first months of life.4

We observed a lower risk of infection among infants born to women who received their third dose in pregnancy compared with the second, suggesting a stronger level of protection following the booster dose. This aligns with studies showing a waning of vaccine effect after the second dose unless a booster is received.11 Infants born to women with only 1 mRNA vaccine dose received during pregnancy also had a lower risk of a positive SARS-CoV-2 test than those born to unvaccinated women, but results were not statistically significant.

Strengths and Limitations

The strengths of this study include the use of registry data covering the whole Norwegian population and many individuals vaccinated during pregnancy. Mandatory reporting to registries (including all COVID-19 vaccinations) limited potential selection bias and provided detailed information on clinical and sociodemographic variables. We believe our study results are generalizable to other pregnant populations. This assumption is strengthened by the fact that the findings align with the results from the US study examining maternal COVID-19 vaccination and risk of infant hospitalization for COVID-19.6

The limitations of this study included the lack of information on the infant’s test with a SARS-CoV-2 variant. However, there were distinct periods of dominance with the different variants in Norway during the study period, and we believe the defined periods capture risk with the different variants. The differences we observed in estimates for the Delta and Omicron-dominated periods support this, as the vaccines generally have been shown to be less effective against Omicron than Delta.8,11

Although we did not include vaccinations during the last 14 days of pregnancy or after pregnancy in the vaccinated group to allow for sufficient time of transplacental transfer of antibodies before birth,22 there could be a possible added effect of transfer of SARS-CoV-2 antibodies through breastmilk in these children,23,24 as more than 90% of infants in Norway are breastfed.25,26 We did not have individual-level information on breastfeeding and were unable to directly address whether this differed by maternal vaccination status.

We adjusted for potential confounders, which did not substantially affect the estimates. Still, there may be residual confounding because of healthy vaccinee bias27 or other unmeasured differences in characteristics between women who got vaccinated during pregnancy and those who did not.

The distribution of follow-up time in the vaccinated and unvaccinated groups varied across the 2 periods. We used calendar time as the underlying time scale in the analyses to ensure that comparisons were made on the same calendar days. This was important, as maternal vaccination status and risk of SARS-CoV-2 infection varied substantially over the study period. Although we did not have information on the number of household members or positive SARS-CoV-2 tests among them, we adjusted for maternal parity as a proxy.

We did not have information on disease symptoms in the infants. Thus, we could not assess the severity of the infections and whether this differed by maternal vaccination status. As the number of infants hospitalized for COVID-19 was low, we could not perform robust analyses to discern whether this differed by maternal vaccination status. We found that infants born to unvaccinated women were more likely to be tested for SARS-CoV-2, and this could be because of higher incidence of COVID-19 or a higher likelihood of symptomatic disease leading to testing. Although we cannot exclude differential test behavior according to maternal vaccination status, we believe it is unlikely. However, women who got vaccinated may have behaved differently (ie, taking more or fewer precautions to limit infant infection risk), which could have biased the estimates. Still, this is unlikely to account for all of the substantial reduction in risk that we observed.


In this nationwide registry-based cohort study, we found that infants born to women who received a second or third COVID-19 vaccine dose during the last 2 trimesters of pregnancy had a lower incidence of SARS-CoV-2 infection within the first 4 months of life compared with infants born to unvaccinated women. The reduction in infant infection risk was greater during the Delta-dominated period compared with the Omicron-dominated period. The findings of this study provide early evidence to suggest that infants benefit from passive protection from SARS-CoV-2 infection following maternal COVID-19 vaccination during pregnancy.


1.Cui  X, Zhao  Z, Zhang  T,  et al.  A systematic review and meta-analysis of children with coronavirus disease 2019 (COVID-19).   J Med Virol. 2021;93(2):1057-1069. doi:10.1002/jmv.26398PubMedGoogle ScholarCrossref

2.Campbell  H, Gupta  S, Dolan  GP,  et al.  Review of vaccination in pregnancy to prevent pertussis in early infancy.   J Med Microbiol. 2018;67(10):1426-1456. doi:10.1099/jmm.0.000829PubMedGoogle ScholarCrossref

3.Regan  AK, Munoz  FM.  Efficacy and safety of influenza vaccination during pregnancy: realizing the potential of maternal influenza immunization.   Expert Rev Vaccines. 2021;20(6):649-660. doi:10.1080/14760584.2021.1915138PubMedGoogle ScholarCrossref

4.Abu-Raya  B, Madhi  SA, Omer  SB,  et al.  Global perspectives on immunization against SARS-CoV-2 during pregnancy and priorities for future research: an international consensus paper from the World Association of Infectious Diseases and Immunological Disorders.   Front Immunol. 2021;12:808064. doi:10.3389/fimmu.2021.808064PubMedGoogle ScholarCrossref

5.Flannery  DD, Gouma  S, Dhudasia  MB,  et al.  Assessment of maternal and neonatal cord blood SARS-CoV-2 antibodies and placental transfer ratios.   JAMA Pediatr. 2021;175(6):594-600. doi:10.1001/jamapediatrics.2021.0038
ArticlePubMedGoogle ScholarCrossref

6.Halasa  NB, Olson  SM, Staat  MA,  et al; Overcoming COVID-19 Investigators; Overcoming COVID-19 Network.  Effectiveness of maternal vaccination with mRNA COVID-19 vaccine during pregnancy against COVID-19–associated hospitalization in infants aged <6 months—17 states, July 2021-January 2022.   MMWR Morb Mortal Wkly Rep. 2022;71(7):264-270. doi:10.15585/mmwr.mm7107e3PubMedGoogle ScholarCrossref

7.Rottenstreich  A, Zarbiv  G, Oiknine-Djian  E,  et al.  Timing of SARS-CoV-2 vaccination during the third trimester of pregnancy and transplacental antibody transfer: a prospective cohort study.   Clin Microbiol Infect. 2022;28(3):419-425. doi:10.1016/j.cmi.2021.10.003PubMedGoogle ScholarCrossref

8.Ferdinands  JM, Rao  S, Dixon  BE,  et al.  Waning 2-dose and 3-dose effectiveness of mRNA vaccines against COVID-19–associated emergency department and urgent care encounters and hospitalizations among adults during periods of Delta and Omicron variant predominance—VISION Network, 10 states, August 2021-January 2022.   MMWR Morb Mortal Wkly Rep. 2022;71(7):255-263. doi:10.15585/mmwr.mm7107e2PubMedGoogle ScholarCrossref

9.Norwegian Institute of Public Health.  The COVID-19 Epidemic: Risk Assessment of the Epidemic and the Omicron Variant in Norway. Norwegian Institute of Public Health; 2022.


Adhikari  EH, MacDonald  L, SoRelle  JA, Morse  J, Pruszynski  J, Spong  CY.  COVID-19 cases and disease severity in pregnancy and neonatal positivity associated with Delta (B.1.617.2) and Omicron (B.1.1.529) variant predominance.   JAMA. 2022;327(15):1500-1502. doi:10.1001/jama.2022.4356
ArticlePubMedGoogle ScholarCrossref

11.Andrews  N, Stowe  J, Kirsebom  F,  et al.  Covid-19 vaccine effectiveness against the Omicron (B.1.1.529) variant.   N Engl J Med. 2022;386(16):1532-1546. doi:10.1056/NEJMoa2119451PubMedGoogle ScholarCrossref

12.Norwegian Institute of Public Health. Medical Birth Registry of Norway. Accessed February 16, 2022.

13.Norwegian Institute of Public Health. Emergency preparedness register for COVID-19 (Beredt C19). Accessed February 16, 2022.

14.Trogstad  L, Ung  G, Hagerup-Jenssen  M, Cappelen  I, Haugen  IL, Feiring  B.  The Norwegian immunisation register–SYSVAK.   Euro Surveill. 2012;17(16):17. doi:10.2807/ese.17.16.20147-enPubMedGoogle ScholarCrossref

15.Hall  V, Foulkes  S, Insalata  F,  et al; SIREN Study Group.  Protection against SARS-CoV-2 after Covid-19 vaccination and previous infection.   N Engl J Med. 2022;386(13):1207-1220. doi:10.1056/NEJMoa2118691PubMedGoogle ScholarCrossref

16.Maertens  K, Tran  TMP, Hens  N, Van Damme  P, Leuridan  E.  Effect of prepregnancy pertussis vaccination in young infants.   J Infect Dis. 2017;215(12):1855-1861. doi:10.1093/infdis/jix176PubMedGoogle ScholarCrossref

17.Rottenstreich  A, Zarbiv  G, Oiknine-Djian  E,  et al.  The effect of gestational age at BNT162b2 mRNA vaccination on maternal and neonatal SARS-CoV-2 antibody levels.   Clin Infect Dis. 2022;ciac135. doi:10.1093/cid/ciac135PubMedGoogle ScholarCrossref

18.Norwegian Institute of Public Health. Norwegian Surveillance System for Communicable Diseases (MSIS). Accessed February 16, 2022.

19.Carcione  D, Regan  AK, Tracey  L,  et al.  The impact of parental postpartum pertussis vaccination on infection in infants: a population-based study of cocooning in Western Australia.   Vaccine. 2015;33(42):5654-5661. doi:10.1016/j.vaccine.2015.08.066PubMedGoogle ScholarCrossref

20.Quinn  HE, Snelling  TL, Habig  A, Chiu  C, Spokes  PJ, McIntyre  PB.  Parental Tdap boosters and infant pertussis: a case-control study.   Pediatrics. 2014;134(4):713-720. doi:10.1542/peds.2014-1105PubMedGoogle ScholarCrossref

21.Bakken  IJ, Ariansen  AMS, Knudsen  GP, Johansen  KI, Vollset  SE.  The Norwegian Patient Registry and the Norwegian Registry for Primary Health Care: research potential of two nationwide health-care registries.   Scand J Public Health. 2020;48(1):49-55. doi:10.1177/1403494819859737PubMedGoogle ScholarCrossref

22.Abu-Raya  B, Maertens  K, Edwards  KM,  et al.  Global perspectives on immunization during pregnancy and priorities for future research and development: an international consensus statement.   Front Immunol. 2020;11:1282. doi:10.3389/fimmu.2020.01282PubMedGoogle ScholarCrossref

23.Gray  KJ, Bordt  EA, Atyeo  C,  et al.  Coronavirus disease 2019 vaccine response in pregnant and lactating women: a cohort study.   Am J Obstet Gynecol. 2021;225(3):303.e1-303.e17, e17. doi:10.1016/j.ajog.2021.03.023PubMedGoogle ScholarCrossref

24.Perl  SH, Uzan-Yulzari  A, Klainer  H,  et al.  SARS-CoV-2–specific antibodies in breast milk after COVID-19 vaccination of breastfeeding women.   JAMA. 2021;325(19):2013-2014. doi:10.1001/jama.2021.5782
ArticlePubMedGoogle ScholarCrossref

25.Revheim  I, Balthasar  MR, Akerkar  RR,  et al.  Trends in the prevalence of breastfeeding up to 6 months of age using structured data from routine child healthcare visits.   Acta Paediatr. 2022. doi:10.1111/apa.16367PubMedGoogle ScholarCrossref

26Lande  B, Helleve  A. Breastfeeding and infants’ diet. Accessed April 22, 2022.,35%20%25%20ved%2012%20m%C3%A5neders%20alder

27.Savitz  DA, Fell  DB, Ortiz  JR, Bhat  N.  Does influenza vaccination improve pregnancy outcome? methodological issues and research needs.   Vaccine. 2015;33(47):6430-6435. doi:10.1016/j.vaccine.2015.08.041PubMedGoogle ScholarCrossref

Association Between COVID-19 Booster Vaccination and Omicron Infection in a Highly Vaccinated Cohort of Players and Staff in the National Basketball Association


Caroline G. Tai, PhD, MPH1Lisa L. Maragakis, MD, MPH2Sarah Connolly, PhD, MPH1et alJohn DiFiori, MD3Deverick J. Anderson, MD, MPH4Yonatan H. Grad, MD, PhD5Christina DeFilippo Mack, PhD, MSPH1 JAMA. Published online June 2, 2022. doi:10.1001/jama.2022.9479

Evaluation of COVID-19 vaccine booster effectiveness is essential as new variants of SARS-CoV-2 emerge. Data support the effectiveness of booster doses in preventing severe disease and hospitalization; however, the association with reducing incident SARS-CoV-2 infections is not clear.13 We compared the incidence of SARS-CoV-2 infection in players and staff of the National Basketball Association (NBA) who did vs those who did not receive a booster dose.


Players and staff who were tested more than once between December 1, 2021, and January 15, 2022, were included. Individuals were tested via the nucleic acid amplification test when symptomatic, after a known exposure, or during daily enhanced surveillance testing triggered by multiple cases on 1 team. Player vaccinations were not mandated. Staff were required to be fully vaccinated by October 1, 2021, and to have received a booster dose by January 5, 2022, if eligible. Masking requirements were similar between players and staff, with the exceptions of players unmasking on court and head coaches unmasking during games.

Genome sequencing was performed for all infections to determine the SARS-CoV-2 variant, but some sequencing failed due to inadequate sample volume, viral load, or genome coverage. Vaccination status was considered as a time-varying exposure; individuals could dynamically move through multiple categories during the study and contribute person-days accordingly. Fully vaccinated was defined as 2 doses of a 2-dose vaccination course (Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273) or 1 dose of the 1-dose vaccination course (Johnson & Johnson JNJ-78436735)4 and fully boosted was defined as 14 days after receiving any booster dose.

Hazard ratios (HRs) from an Andersen-Gill Cox proportional hazards model5 compared time to infection for individuals who were fully vaccinated vs those who were fully boosted. Infections occurring after vaccination but prior to 14 days after vaccination were censored. The outcomes included confirmed SARS-CoV-2 infections, symptomatic infections, COVID-19 hospitalizations, and COVID-19 deaths.

The models were adjusted for age and prior SARS-CoV-2 infection and the analyses were performed using SAS version 8.2 (SAS Institute Inc) and R version 4.1.1 (R Foundation for Statistical Computing). Statistical significance was defined as a 2-sided P < .05. The Advarra institutional review board determined the study met criteria for exemption status. Individuals signed health information authorizations allowing collection, storage, and use of health information by the NBA for monitoring purposes, including disclosure to medical experts.


Of 2613 players and staff, 67% were followed up the entire 45-day study period, with 74 165 person-days contributed by fully boosted individuals and 10 890 person-days by those who were fully vaccinated but not boosted though eligible to receive a booster dose. From the start to the end of the study period, the percentage of individuals who were fully vaccinated and eligible for a booster dose decreased from 26% (n = 682) to 8% (n = 205) and the percentage of individuals who were fully boosted increased from 49% (n = 1282) to 85% (n = 2215); the remainder were in other categories, such as fully vaccinated but not yet eligible for a booster or within 14 days of their booster dose. In the overall cohort, 88% were male with a median age of 33.7 years (IQR, 27.3-45.2 years; Table 1).

Individuals who were fully boosted experienced 608 confirmed SARS-CoV-2 infections and were significantly less likely to be infected than fully vaccinated individuals who were booster eligible and had not received a booster, who had experienced 127 confirmed infections (adjusted HR, 0.43 [95% CI, 0.35-0.53], P < .001; Table 2). The secondary analyses evaluating symptomatic infection showed a similar association (adjusted HR, 0.39 [95% CI, 0.30-0.50]; P < .001). No hospitalizations or deaths occurred. Omicron was the dominant variant, representing 93% of 339 sequenced cases.


This study found that in a young, healthy, highly vaccinated cohort frequently monitored for SARS-CoV-2, booster vaccination was associated with a significant reduction in incident infections during the Omicron wave. Study limitations include generalizability to older populations and the possibility that some infections may have been undetected in the absence of daily surveillance testing. This is a population that was recently boosted (median of 20 days as of December 1, 2021) and may not reflect waning efficacy over time. Surveillance testing in this population captured both symptomatic and asymptomatic infections, which differs from studies of the effectiveness of boosters that did not assess risk of asymptomatic infections.2,3 Continued research is required to assess the need for additional booster doses beyond a single booster dose.


1.Johnson  AG, Amin  AB, Ali  AR,  et al.  COVID-19 incidence and death rates among unvaccinated and fully vaccinated adults with and without booster doses during periods of Delta and Omicron Variant Emergence—25 US jurisdictions, April 4-December 25, 2021.   MMWR Morb Mortal Wkly Rep. 2022;71(4):132-138. doi:10.15585/mmwr.mm7104e2PubMedGoogle ScholarCrossref

2.Thompson  MG, Natarajan  K, Irving  SA,  et al.  Effectiveness of a third dose of mRNA vaccines against COVID-19–associated emergency department and urgent care encounters and hospitalizations among adults during periods of Delta and Omicron variant predominance—VISION Network, 10 states, August 2021-January 2022.   MMWR Morb Mortal Wkly Rep. 2022;71(4):139-145. doi:10.15585/mmwr.mm7104e3PubMedGoogle ScholarCrossref

3.Accorsi  EK, Britton  A, Fleming-Dutra  KE,  et al.  Association between 3 doses of mRNA COVID-19 vaccine and symptomatic infection caused by the SARS-CoV-2 Omicron and Delta variants.   JAMA. 2022;327(7):639-651. doi:10.1001/jama.2022.0470
ArticlePubMedGoogle ScholarCrossref

4.US Centers for Disease Control and Prevention. Stay up to date with your vaccines. Accessed April 10, 2022.

5.Andersen  PK, Gill  RD.  Cox’s regression model for counting processes: a large sample study.   Ann Stat. 1982;10(4):1100-1120. doi:10.1214/aos/1176345976Google ScholarCrossref

How many times can you get COVID? What experts know about reinfection

Authors:  Hannah Sparks May 18, 2022  The New York Post

The new normal is now.

In what seemed like an instant, COVID-19 became an inevitable aspect of everyday life more than two years ago — with no signs to suggest that we’ll ever see otherwise again.

As we look at our lives ahead with waves of new variants and “stealth” sub-variants, and seasonal vaccine boosters to match, it begs the question: Should we fear reinfection?

Doctors have recently confirmed that those infected with an earlier Omicron variant, which first appeared and spread rapidly last summer, can indeed test positive again for the new sub-variant.

Last week, as the latest strain — BA.2 or BA2.12.1 — made its presence known in New York City and clusters throughout the Northeast and Midwest, the US crossed a grim milestone: 1,000,000 COVID deaths. Globally, we’ve lost more than 6,000,000.

The Post spoke to NYU Langone Health infectious diseases expert Dr. Michael Phillips about what we can expect from life with COVID as we know it.

Can you get infected with COVID twice — and who’s at risk?

There is no such thing as perfect immunity from COVID. Regardless of severity or immunization, someone who tests positive for the virus can become infected again at some point.

“Our hospitalizations have crept up over the past several weeks, particularly with this newer variant of Omicron,” Dr. Phillips told The Post. “But thankfully, the vast majority of people [who] get the infection tend to recover without too much problems.”

But there’s more at stake for some. People who have not received two doses of the mRNA vaccine, as well as those with weakened immune systems due to age, medications, preexisting illness or other clinical factors, such as poor physical fitness, are at a higher risk of reinfection and becoming severely sick with COVID-19.

But Phillips warns against us “develop[ing] a laissez faire attitude about it.” While some relatively young, healthy and vaccinated individuals may become reinfected with only a mild case, the person they pass it to — potentially, someone with a weakened immune system due to age, medications, preexisting illness or other clinical factors, such as poor physical fitness — may not fare so well.

Omicron is “very, very different from prior waves of Delta,” Phillips added. “I think it shifted our game plan for sure.” Now more than ever the focus of prevention efforts is on protecting those the ones at a greater risk of severe illness — and protecting yourself from COVID reinfection means also “protect[ing] the vulnerable.”

Can you be reinfected with the same COVID variant?

It’s certainly possible, particularly in those who are not vaccinated. Unlike earlier variants, Omicron has rapidly evolved into several sub-types, prompting simultaneous localized outbreaks. Meanwhile, there’s no telling how many positive cases of COVID-19 go unreported, whether due to lack of testing or symptoms to warrant alarm. So whether to fear reinfection with the same niche strain may not be a pragmatic question to ask — because, by the time it’s answered, a new strain may already be here.

“There are so many of these other variants within that big family of coronaviruses, and we’re typically infected with three to four a year,” Phillips explained, most of which present as a mild cold.

Ideally, SARS-CoV-2 could fade into coronavirus obscurity like many of the others — but we aren’t there yet, and it’s too soon to say whether that’s a feasible outlook. “It’s still severe enough that that we have to be pretty mindful about,” said Phillips. “We just don’t know enough about future variants for us to take our guard down yet.”

How long after getting COVID can you be reinfected?

This is another complicated question — especially for sufferers of long COVID, who appear to harbor low, even undetectable levels of the virus for weeks and months. For mild to moderate cases, people who test positive for COVID can expect their infection to clear within five to 10 days after their symptoms arose, or since their confirmed test result.

Nascent research suggests that the average immune system can fend off COVID reinfection for three to five months after the previous bout. That’s why, according to the Centers for Disease Control and Prevention, people who had a confirmed infection within the previous 90 days are not expected to quarantine after coming in contact with another infected individual.

But all bets are off about six months later, when antibodies are known to start waning — regardless of vaccination.

How long do COVID antibodies last?

Experts don’t know exactly. While those survive COVID appear to be largely protected from repeat or severe illness for up to five months after the previous infection, there isn’t enough data available yet to be certain how long those COVID-specific antibodies linger, or even to confirm that the presence of antibodies guarantees immunity, according to the Food and Drug Administration.

Immune system B cells give rise to COVID-specific antibodies, designed to attack the virus on sight, before it can penetrate tissue cells and reproduce. They begin to form within the first few days infection or vaccination, and continue to build for several weeks until they peak at around three months thereafter — when your COVID defenses are at their strongest.

The good news is that waning antibodies doesn’t mean we’re totally defenseless, as some B cells will remember the tools it previously took to create COVID antibodies during re-invasion. (Boosters, furthermore, helps our immune system remember how. to fight.) Meanwhile, our killer T-cells, the immune system’s backup line of defense, may not so good at preventing the virus from entering the body, but they can spot an infected host cell — and destroy before it multiplies to another cell. And while they’re more difficult to track, they do appear to be more faithful than fleeting antibodies.

“Those appear to stay be much more robust,” said Phillips, adding, that “the T cell response is probably more important for response to viral infections” in the long run.

Are COVID vaccines still effective?

“We don’t have to be paranoid about the emergence of a new strain … but we have to be thoughtful and ready for that.”

Dr. Michael Phillips, MD, NYU Langone Health

More or less. Vaccines remain the best way to build-up antibodies, the body’s primary line of defense against severe COVID-19 illness. While allowing oneself to become infected can also give rise to antibodies, it’s not worth the risk.

“I’m strongly pro vaccine, because of the the problems that happen when you don’t get it,” said Phillips, who hinted at alternative forms of vaccination technology on the horizon as well.

Regardless of type, antibodies are known to wane afer about six months since last infection or booster, making reinfection more likely to occur.

How often can you get a COVID booster?

For those on the two-dose regimen, a second round should be completed about six weeks after the first. However, it’s been well over a year since the vaccine was introduced, which means many patients completed those two rounds back in 2021.

Doctors expect that annually, even seasonally redesigned boosters against COVID-19 could become the norm — kind of like influenza, only different, and more troubling: One flu season sees just one or two major strains globally, allowing researchers time to prepare vaccines. “It’s not this, sort of, constant changing during a ‘season’,” said Phillips, like COVID-19 has done.

Currently, only those who have a weakened immune system and people age 50 or older are being recommended for a third shot by the CDC — which is, altogether, a good sign.

Said Phillips, “We don’t have to be paranoid about the emergence of a new strain … but we have to be thoughtful and ready for that.”

What You Should Know About Treating Covid-19

Some therapies have been shown to work in clinical studies and other research

Authors: Jared S. Hopkins Mar. 21, 2022 4:47 pm ET The Wall Street Journal

The Food and Drug Administration authorized the first antiviral pills to treat Covid-19 from Pfizer Inc. and Merck & Co. and partner Ridgeback Biotherapeutics LP in December. The authorizations came after each drugmaker’s pill received a positive recommendation from a panel of experts advising the FDA, and weeks after the emergence of the Omicron variant.

Public-health experts say the best preventive measure to decrease the likelihood of contracting Covid-19 is to get vaccinated. The Centers for Disease Control and Prevention has recommended that everyone 12 and older get an additional shot after completing a primary series of Covid-19 vaccination.

Here’s what public-health and infectious-disease experts say about how to treat Covid-19.

I’ve contracted Covid-19; what should I do? How can I treat mild symptoms from home?

Doctors say an initial step is to monitor symptoms to determine whether infected people could be considered at low or high risk for developing severe disease. Individuals who are typically considered to be at low risk for severe disease include people who are young and healthy. They should stay at home away from others, drink plenty of fluids to stay hydrated and take over-the-counter medicines such as acetaminophen or ibuprofen to reduce fevers, according to physicians and the CDC. Physicians say people who are young, otherwise healthy and at low risk of developing severe disease should recover if they take the right steps. 

People who are at high risk include those with underlying health conditions and the elderly, according to doctors. These individuals should pay close attention to any change in their health, including symptoms of fever, cough, fatigue or difficulty breathing. If high-risk individuals need medical attention, they should seek it right away.

“The management of Covid continues to depend on what your risk of progression is,” said Carlos del Rio, a professor of global health at Emory University. “Treatment has to be individualized.” 

Additionally, people who are vaccinated and become infected—what is known as a breakthrough case—are unlikely to develop severe disease or need hospitalization, according to doctors and studies.

What are Covid-19 antiviral pills? When can I get one to treat myself?

Antivirals are treatments designed to impede a virus’s replication cycle, allowing people to recover from the illness, and they are most effective if they are taken by patients early in the course of disease. 

Merck and partner Ridgeback say their oral antiviral, molnupiravir, reduced the risk of hospitalization and death by about 30%. Pfizer said in December a late-stage study confirmed its oral antiviral, called Paxlovid, which is taken with another antiviral called ritonavir, was 89% effective at reducing the risk of hospitalization and death in adults at high risk of severe Covid-19. A separate, preliminary analysis found that the drug may also help people at low risk of severe Covid-19. The company said lab tests showed Paxlovid works against the Omicron variant. 

Both drugs are authorized by the FDA, and have been cleared for use. 

The pills carry some safety risks and limitations. A component of Pfizer’s Paxlovid regimen, ritonavir, can interact with other drugs in dangerous or life-threatening ways. Drugs that interact with Paxlovid include common ones such as the cholesterol-lowering pill simvastatin, the antipsychotic lurasidone and the sedative triazolam. Patients should make sure to tell their doctor or pharmacist of any medications they take before starting an antiviral regimen from Pfizer, according to physicians. The Merck-Ridgeback drug isn’t authorized for children because of its potential effect on bone and cartilage growth. It isn’t recommended for pregnant women because of the potential for fetal harm, a safety signal seen in animal studies of the drug.

The Merck-Ridgeback drug can be prescribed by doctors to adults at high risk of severe disease shortly after they develop mild to moderate symptoms. Pfizer’s drug permits doctors to prescribe the medicine to high-risk patients age 12 and older early in the course of disease, shortly after they develop symptoms.

The companies studied their drugs in people who are at high risk of developing severe disease. They excluded certain people from their tests: Both left out pregnant women while Pfizer excluded people who take certain common medications such as heart drugs. 

The pills are also being tested in people for preventive use with results expected by mid-2022.

Both treatments are taken over five days, with Pfizer’s totaling 30 pills and Merck-Ridgeback clocking in at 40 capsules. 

The U.S. has purchased 20 million courses of treatment of Pfizer’s pill, although supply has been limited as the company increases manufacturing. The government purchased about 3.1 million courses of the Merck-Ridgeback pill, and Merck said all of it has been supplied.

Will antiviral pills be effective against the Omicron variant?

The antiviral manufacturers say they expect the treatments to be effective against Omicron, although they plan to conduct tests to verify. Both drugs target different parts of the virus than vaccines and other treatments, which are targeting the spike protein that plays a key role in infecting cells. 

Pfizer has said so far its researchers haven’t seen any changes in the variant that suggests Paxlovid, which is given with the antiviral ritonavir, is less effective than against previous strains. The company said in January that three separate lab tests showed Paxlovid is effective against the Omicron.

Merck said last year that it was working to collect samples of Omicron to study whether molnupiravir is effective against Omicron and expected results by the end of the year. It has not announced results from any internal testing

Molnupiravir targets machinery the virus uses to replicate, rather than the spike protein, the structure that helps the virus infiltrate cells.

Merck expects molnupiravir to be effective against Omicron because testing has found the drug to be effective against other circulating variants. “Molnupiravir retains activity across all of these variants of concern, and there’s no difference in its antiviral activity,” said Daria Hazuda, vice president of infectious disease discovery at Merck. “There shouldn’t be any more or less concern about its effectiveness against Omicron versus any other variants.”

Merck and partner Ridgeback said in January that molnupiravir was active against Omicron in laboratory tests, pointing to six preclinical studies performed by researchers outside the company.

Are there any drugs approved or authorized for administration in clinics?

Monoclonal antibody treatments are available for people who develop symptoms and are considered to be at high risk of severe disease. As many as 75% of U.S. adults are eligible to take the drugs under FDA guidelines, according to experts. The drugs are lab-engineered molecules that mimic the natural antibodies produced by the immune system to fight off viruses. They are usually administered by infusion or injection at hospitals or clinics.

“It’s a lot easier to access one of these if you happen to live in a more populous area,” said Erica Johnson, chair of the Infectious Disease Board of the American Board of Internal Medicine and assistant professor of infectious diseases at Johns Hopkins University School of Medicine.

The FDA is permitting use of antibody treatments from Eli Lilly & Co., and from GlaxoSmithKline PLC and partner Vir Biotechnology. In January the agency restricted use of older antibody drugs from Lilly and Regeneron Pharmaceuticals because tests found they lost potency against the Omicron variant.

The Glaxo-Vir drug, sotrovimab, has retained effectiveness against Omicron. Regulators cleared for use in February a new drug from Lilly called bebtelovimab that retains effectiveness against Omicron, for the treatment of mild to moderate Covid-19 in nonhospitalized individuals 12 and older who are at high risk of getting severely sick.

In some parts of the U.S., the antibody treatments may be available for administration at home or through mobile clinics. Some states are also allowing low-risk patients to receive monoclonal antibodies, but it is not recommended by the National Institutes of Health. “The juice is not worth the squeeze,” Dr. del Rio said. 

Evusheld, a preventive antibody cocktail from AstraZeneca PLC, which has shown strong efficacy in reducing risk of symptomatic Covid-19, was authorized by the FDA on Dec. 8. Evusheld is delivered as two shots and aims to offer an alternative to vaccines primarily for a minority of adolescents and adults age 12 and older with moderate to severely compromised immune systems. That includes those who have cancer, another illness, or take medications or undergo treatments such as chemotherapy that inhibit an immune response to Covid-19 vaccines.

The FDA in January permitted the use of Veklury, also known as remdesivir, for treatment of people who are not hospitalized with Covid-19. The antiviral was first developed for treating Ebola

For patients with mild to moderate symptoms but who are at high risk of developing severe disease and becoming hospitalized, the National Institutes of Health says the first option should be Paxlovid. If the drug is unavailable, or the patient can’t take it for some reason, sotrovimab should be administered. Veklury is the third option, followed by molnupiravir.

My loved one is hospitalized. Are there any FDA-approved treatments for hospitalized Covid-19 patients?

Most research has found that monoclonal antibodies aren’t effective once people become hospitalized and they are currently not recommended at that point.

Veklury is fully approved for treatment of people who are hospitalized with Covid-19.

Patients who may be at risk of advancing to severe disease may also be given dexamethasone, a steroid first approved in the 1950s that is successful at treating inflammation. The steroid has been found in studies of hospitalized Covid-19 patients to reduce the risk of death. It is recommended for treatment by the NIH and the Infectious Diseases Society of America. 

Patients who don’t respond to dexamethasone may be given an immune-suppressing rheumatoid arthritis drug called Olumiant, which received an emergency-use authorization from the FDA after a study showed it helped hospitalized patients recover more quickly.

A similar rheumatoid arthritis drug, Actemra, made by Roche Holding AG, is also used to tamp down the potentially lethal inflammation seen in some hospitalized patients.

Doctors sometimes administer blood-thinners to hospitalized patients, which can reduce blood clots and inflammation that develop in some Covid-19 patients. Some studies have found that such treatments can also reduce the risk of patients needing mechanical ventilation and could help them leave the hospital sooner.

Which Covid-19 treatments are being tested?

Bristol-Myers Squibb Co. is testing a monoclonal antibody and expects Phase 2 results in the coming months, according to the company.

Researchers studying the antidepressant fluvoxamine recently reported in the Lancet, a peer-reviewed medical journal, that patients who took the widely available drug were significantly less likely to require hospitalization than those who didn’t. The drug is still being studied, and isn’t yet recommended by the NIH or IDSA. 

Some research has suggested steroid inhalers are helpful at reducing symptoms early in the course of the disease, said David Boulware, an infectious-diseases specialist at the University of Minnesota. He said it is unlikely manufacturers would seek an emergency use authorization because they are widely available, although the NIH and IDSA hasn’t recommended them.

An oral antiviral from Japanese drugmaker Shionogi & Co. is also in clinical trials.

Is ivermectin effective in treating Covid-19?

In the latest trial, researchers testing the antiparasitic drug ivermectin against Covid-19 found that the drug didn’t reduce hospital admissions. The trial, with nearly 1,400 Covid-19 patients at risk of severe disease, is the largest to show that those who received ivermectin as a treatment didn’t fare better than those who received a placebo.

Most prior research hasn’t shown that ivermectin is an effective Covid-19 treatment, physicians say, and the drug isn’t authorized for that use. The FDA has approved ivermectin to treat some parasitic worms, as well as a topical treatment for head lice and skin conditions such as rosacea. It is also used in the U.S. to treat or prevent parasites in animals.

The drug, which was developed years ago by Merck, has been used to prevent river blindness and other diseases in Africa and other places where parasites are common. Prescriptions of the drug have shot up in recent months, and federal health regulators have warned doctors and veterinarians against the unauthorized use of ivermectin to treat Covid-19. 

Can my doctor treat me with hydroxychloroquine?

Numerous studies have found that hydroxychloroquine and chloroquine, approved decades ago to treat and prevent malaria, don’t reduce the severity of Covid-19 symptoms or provide a benefit to patients. Doctors, however, are permitted to write so-called off-label prescriptions, to treat ailments that the FDA hasn’t approved, and some doctors have done so with hydroxychloroquine and chloroquine. 

The drugs, which are also used to treat ailments such as lupus and rheumatoid arthritis, initially received emergency-use authorization, although the FDA later revoked it after concluding the therapies were unlikely to help fight the disease. 

Early in the pandemic hospitals and doctors around the world began treating Covid-19 patients with hydroxychloroquine after several small studies suggested a benefit.

The NIH recommends against the use of hydroxychloroquine in hospitalized or nonhospitalized people, as does the IDSA, which also recommends against it as a prophylactic. 

I’m vaccinated but I contracted Covid-19. Can I use any of the approved treatments?

“Vaccination remains one of the most important factors for us to consider,” said Dr. Abhijit Duggal, a staff ICU physician and director for critical care research for the medical ICU at the Cleveland Clinic. “Anything that we do after that is really trying to minimize the damage associated with the viral infection.”

He said factors that affect treatment decisions in vaccinated people included whether someone has any underlying immunity as well as any comorbidities. Doctors say that while it remains unlikely that vaccinated people will end up in the hospital, those who do will likely be eligible for similar treatments. 

“Once you get hospitalized in breakthrough cases you will get all the usual therapies,” Dr. Duggal said. “Vaccination not only prevents the disease but also ameliorates the severity of disease.” He said some doctors in the U.S. have administered antibody treatments but it isn’t standard treatment and may not be appropriate since the virus infected the patient despite the presence of antibodies from the vaccines. 

What if I am immunocompromised and become infected?

Most of the hospitalized patients who were previously vaccinated are immunocompromised, according to doctors. Hospitalized patients who are immunocompromised are eligible to receive convalescent plasma, a highly concentrated solution of antibodies taken from recovered Covid-19 patients. There is limited data that suggests monoclonal antibody treatments will benefit the immunocompromised, even if they are vaccinated, said Dr. Duggal. 

—Joseph Walker contributed to this article.

Israeli experts analyze mRNA COVID vaccines long-term effects

Experts believe there will be no long-term side effects to the mRNA vaccines.

Authors: By MAAYAN JAFFE-HOFFMAN   AUGUST 30, 2021 22:34

As thousands of Israelis rush back to their health funds in search of a third COVID-19 vaccine shot and a Green Pass from isolation after traveling abroad, others are asking if another injection of messenger RNA is safe.The American Food and Drug Administration provided full approval of the Pfizer coronavirus vaccine last week, but noted in its press release that “information is not yet available about potential long-term health outcomes.”However, Tal Brosh, head of the Infectious Disease Unit at Samson Assuta Ashdod University Hospital, told The Jerusalem Post that while he cannot claim to know what is going to happen in 10 years, “there is no true reason to think there are any significant long-term effects” of the vaccine.He explained that there is no other vaccine that was evaluated for a decade before approval and that there is not an example of another vaccine – although no other vaccine is an mRNA vaccine – that has been linked to any significant long-term effects.“There is no evidence of something happening unless it happened in the first two hours, two weeks or two months,” said Michal Linial, a professor of biological chemistry at the Hebrew University of Jerusalem. “We do not know of any other examples in which the immune system decided to suddenly react to a vaccine that was given 15 years prior.”THERE ARE also few examples of people being nervous about taking a booster shot of an already approved vaccine.If a person were to get cut by rusted metal and go to a doctor, the health professional would probably tell that individual to get a tetanus booster shot. It is unlikely this person would ask the doctor if the booster was safe or if it could prevent her from getting pregnant or him from making babies.“This is the same thing,” Linial said. “I can understand in the beginning that this was a breakthrough and people were shocked, like it is some kind of satellite to the Moon and they don’t want to be the first on the satellite. But now we know: This is nothing like that.”Rather, more than two billion people worldwide have been inoculated against COVID-19 with more than five billion doses. Around 210 million Pfizer mRNA doses have been distributed in America, for example. In Israel, more than 8.5 million doses have been administered. While traditional vaccines generally put a weakened or inactivated germ into our bodies, according to the Centers for Disease Control and Prevention, mRNA vaccines “teach our cells how to make a protein – or even just a piece of a protein – that triggers an immune response inside our bodies. That immune response, which produces antibodies, is what protects us from getting infected if the real virus enters our bodies.”Brosh said that this does not mean that the vaccine changes people’s genetic code. Rather, he said the mRNA is more like a USB device that is inserted into a computer: It does not impact the hard drive of the computer but runs a certain program.“ Messenger RNA is a very fragile molecule, meaning it can be destroyed very easily,” Linial explained. “If you put mRNA on the table, for example, in a minute there will not be any mRNA left. This is as opposed to DNA, which is as stable as you get. ”She said that this fragility is true of the mRNA of any living thing, whether it belongs to a plant, bacteria,

WHILE THE Moderna and Pfizer vaccines are based on new technologies, they are asking our bodies to do something they do every day: cells synthesizing protein. Moderna and Pfizer are simply delivering a specific mRNA sequence to our cells. Once the mRNA is in the cell, human biology takes over. Ribosomes read the code and build the protein, and the cells express the protein in the body. This is one of the main reasons to believe there will be no long-term consequences to the vaccine, said Prof. Eyal Leshem, director of Sheba Medical Center’s Center for Travel Medicine and Tropical Diseases. While the Pfizer and Moderna vaccines are the first mRNA ones to ever be brought to market for human patients, Linial said she believes the reason that no mRNA vaccine has been developed until now is because there was just no need to move this fast on a vaccine until COVID-19 came along. In fact, scientists have been experimenting with mRNA for the better part of the last three decades. Leshem said mRNA vaccines for other diseases, including cancer, have been tested in humans for around 10 years and “no long-term effects were registered” in those trials – though he admitted that these trials generally included small numbers of participants. Individuals began receiving mRNA vaccines against COVID-19 as early as July of last year, and adverse effects have been closely tracked worldwide since then. In Israel, the first vaccines were administered on December 20, 2020.“There is more data on the adverse events of these vaccines than we have ever had on any other vaccine,” Brosh said, adding that no vaccine has ever been given to so many people so quickly. Most adverse events were simple “reactogenicity” – reactions that occur soon after vaccination and that are a physical manifestation of the inflammatory response. These can include fever, muscle pain, swelling at the site of injection or swelling of the lymph nodes, for example – all symptoms that can generally be treated with paracetamol or the like. THE VACCINE was linked to one “immune-mediated phenomenon,” said Brosh, and that is myocarditis – inflammation of the heart muscle – which was the predominant serious side effect in young male adults between the ages of 16 and 25. But even then, myocarditis was rare, generally mild, and those people who developed it fully recovered, he said. Moreover, unvaccinated people who contracted COVID-19 were four times more likely to develop myocarditis than vaccinated people were, according to a new study by Clalit Health Services together with Harvard University that was published last week in the New England Journal of Medicine. The study found that there were around 2.7 cases of myocarditis per 100,000 vaccinated people infected with the virus, compared with 11 cases per 100,000 unvaccinated people who were infected. In general, the study showed that individuals who take the Pfizer coronavirus vaccine may suffer from four out of up to 25 clinically relevant side effects: myocarditis, swelling of the lymph nodes, appendicitis and herpes zoster.In contrast, high rates of multiple serious adverse events were associated with coronavirus infection among unvaccinated patients, including a greatly increased risk of developing myocarditis, pericarditis, arrhythmias, heart attacks, strokes, pulmonary embolism, deep-vein thrombosis or acute kidney damage.“So, all together we know the vaccines are safe and effective. This holds true for the initial doses and probably also for the booster doses,” Leshem said. Linial said she believes that most future vaccines will be made of mRNA because “it is an easy, great technology – no question.” She also said that vaccination is the only way to beat this pandemic. “If people want to go back to their lives,” Linial said, “the population must be vaccinated.” 

Walking down the memory lane with SARS-CoV-2 B cells

Authors: Natalia T FreundMotti GerlicBen A Croker

The end of the coronavirus disease 2019 (COVID-19) pandemic is in sight. We have scientists to thank for that. However, while years of meticulous research by vaccinologists, molecular biologists and immunologists provided the framework for rapid deployment of vaccines, we are still learning what constitutes an effective lifelong immune response to pathogens. A more detailed understanding of human B-cell development and the nature of the antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or immunization may aid vaccine development for known pathogens and further reduce vaccine development times in the event of future pandemics.

Neutralizing antibodies are produced upon infection with SARS-CoV-2,12 but the transition to lifelong immunity awaits ongoing studies, and is of central importance to ending COVID-19. Immunological memory is the pillar by which vaccines offer education to our immune system to protect us from future exposure to pathogens, yet the nature and length of this memory vary. Some natural infections and vaccines provide a lifelong lesson to the immune system, thereby enabling it to “remember” pathogens and antigens for decades, while in other cases the immune system “forgets” the exposure, leading to a waning immune response over months to years. With the advent of vaccines against SARS-CoV-2, along with the emergence of variants of concern, understanding the nature and duration of protective immunity is key to SARS-CoV-2 eradication or, at least, minimalization of severe infections leading to hospitalization and death.

To study long-term immunity to SARS-CoV-2 infection and vaccination, Wang et al.3 have investigated memory B-cell responses to SARS-CoV-2 for a 12-month period in convalescent individuals, some of whom received a COVID-19 messenger RNA (mRNA) vaccine. SARS-CoV-2 convalescent individuals are advised to receive one dose, and in some countries two doses, of a COVID-19 vaccine to increase titers of SARS-CoV-2 antibodies to a level considered effective at virus neutralization. This recent study enables a longitudinal comparison of the natural B-cell response with infection, with and without a supplemental COVID-19 vaccine.

For More Information:

Swedish Professor Says 5 Shots Of COVID Vaccine May Be Necessary

While many people have bragged about being “fully vaccinated” after taking two COVID-19 jabs, a Swedish professor says that as many as five shots may be needed to combat falling immunity.

“We don’t know how long the vaccine protects against serious illness and death,” said Karolinska Institute Professor Matti Sällberg.

“This means that you pick the safe before the unsafe.”

Numerous European countries are planning a 3rd round of COVID “booster shots” in September, and the FDA also indicated that vaccinated individuals will be given another shot in the fall.

However, Sällberg suggests this probably won’t be enough and that “recurring shots” will be necessary.

“After receiving the second dose, the immune response slowly subsides. Within a year, many may have lost their protection. We do not know yet, but if you get a third dose, it will be activated again,” he said.

“Biology says that a fading immune response is not unlikely. Then it’s time for a third, fourth, maybe fifth dose”.

For More Information:

Review the safety of Covid-19 mRNA vaccines: a review

Authors: Pratibha Anand 1Vincent P Stahel 2


The novel coronavirus disease 2019 (COVID-19) has infected more than 100 million people globally within the first year of the pandemic. With a death toll surpassing 500,000 in the United States alone, containing the pandemic is predicated on achieving herd immunity on a global scale. This implies that at least 70-80 % of the population must achieve active immunity against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), either as a result of a previous COVID-19 infection or by vaccination against SARS-CoV-2. In December 2020, the first two vaccines were approved by the FDA through emergency use authorization in the United States. These vaccines are based on the mRNA vaccine platform and were developed by Pfizer/BioNTech and Moderna. Published safety and efficacy trials reported high efficacy rates of 94-95 % after two interval doses, in conjunction with limited side effects and a low rate of adverse reactions. The rapid pace of vaccine development and the uncertainty of potential long-term adverse effects raised some level of hesitation against mRNA vaccines in the global community. A successful vaccination campaign is contingent on widespread access to the vaccine under appropriate storage conditions, deployment of a sufficient number of vaccinators, and the willingness of the population to be vaccinated. Thus, it is important to clarify the objective data related to vaccine safety, including known side effects and potential adverse reactions. The present review was designed to provide an update on the current state of science related to the safety and efficacy of SARS-CoV-2 mRNA vaccines.

For More Information:

Safety of SARS-CoV-2 vaccines: a systematic review and meta-analysis of randomized controlled trials

Authors: Musha ChenYue YuanYiguo ZhouZhaomin DengJin ZhaoFengling FengHuachun Zou & Caijun Sun 


Various modalities of vaccines against coronavirus disease 2019 (COVID-19), based on different platforms and immunization procedures, have been successively approved for marketing worldwide. A comprehensive review for clinical trials assessing the safety of COVID-19 vaccines is urgently needed to make an accurate judgment for mass vaccination.

A systematic review and meta-analysis was conducted to determine the safety of COVID-19 vaccine candidates in randomized controlled trials (RCTs). Data search was performed in PubMed, Embase, Cochrane library, Scopus, Web of Science, and MedRxiv. Included articles were limited to RCTs on COVID-19 vaccines. A total of 73,633 subjects from 14 articles were included to compare the risks of adverse events following immunization (AEFI) after vaccinating different COVID-19 vaccines. Pooled risk ratios (RR) of total AEFI for inactivated vaccine, viral-vectored vaccine, and mRNA vaccine were 1.34 [95% confidence interval (CI) 1.11–1.61, P < 0.001], 1.65 (95% CI 1.31–2.07, P < 0.001), and 2.01 (95% CI 1.78–2.26, P < 0.001), respectively. No significant differences on local and systemic AEFI were found between the first dose and second dose. In addition, people aged ≤ 55 years were at significantly higher risk of AEFI than people aged ≥ 56 years, with a pooled RR of 1.25 (95% CI 1.15–1.35, P < 0.001).


The safety and tolerance of current COVID-19 vaccine candidates are acceptable for mass vaccination, with inactivated COVID-19 vaccines candidates having the lowest reported AEFI. Long-term surveillance of vaccine safety is required, especially among elderly people with underlying medical conditions.

For More Information: