MDedge Infectious Disease

Vaginal cleansing showed no reduction in morbidity when performed before unscheduled cesarean deliveries, researchers reported at the 2022 Pregnancy Meeting of the Society for Maternal-Fetal Medicine.

Several studies have evaluated vaginal cleansing prior to cesarean delivery, with mixed results. The American College of Obstetricians and Gynecologists recommends clinicians consider cleansing prior to unscheduled cesareans, but that advice appears not to be widely heeded.

The new findings, from what the researchers called the single largest study of vaginal cleansing prior to cesarean delivery in the United States, showed no difference in post-cesarean infections when the vagina was cleansed with povidone-iodine prior to unscheduled cesarean delivery.

“These findings do not support routine vaginal cleansing prior to unscheduled cesarean deliveries,” lead author Lorene Atkins Temming, MD, medical director of labor and delivery at Atrium Health Wake Forest School of Medicine, Charlotte, North Carolina, told this news organization. The research was conducted at and sponsored by Washington University School of Medicine, St. Louis, where Dr. Temming did her fellowship.

Dr. Temming’s group compared vaginal cleansing with povidone-iodine in addition to routine abdominal cleansing to abdominal cleansing alone. Among the primary outcomes of the study was the effect of cleansing on post-cesarean infectious morbidity.

“There is a higher risk of infectious complications after cesarean delivery than other gynecologic surgeries,” Dr. Temming told this news organization. “While the reason for this isn’t entirely clear, it is thought to be because cesareans are often performed after a patient’s cervix is dilated. This dilation can allow normal bacteria that live in the vagina to ascend into the uterus and can increase the risk of infections.”

Patients undergoing cesarean delivery after labor were randomly assigned to undergo preoperative abdominal cleansing only (n = 304) or preoperative abdominal cleansing plus vaginal cleansing with povidone-iodine (n = 304). Women were included in the analysis if they underwent cesareans after regular contractions and any cervical dilation, if their membranes ruptured, or if they had the procedure performed when they were more than 4 cm dilated.

The primary outcome was composite infectious morbidity, a catchall that included surgical-site infection, maternal fever, endometritis, and wound complications within 30 days after cesarean delivery. The secondary outcomes were hospital readmission, visits to the emergency department, and treatment for neonatal sepsis.

The researchers observed no significant difference in the primary composite outcome between the two groups (11.7% vs. 11.7%, P = .98; 95% confidence interval, 0.6-1.5). “Vaginal cleansing appears to be unnecessary when preoperative antibiotics and skin antisepsis are performed,” Dr. Temming said.

Jennifer L. Lew, MD, an ob/gyn at Northwestern Medicine Kishwaukee Hospital in Dekalb, Illinois, said current practice regarding preparation for unscheduled cesarean surgery includes chlorhexidine on the abdomen and povidone-iodine for introducing a Foley catheter into the urethra.

“Many patients may already have a catheter in place due to labor and epidural, so they would not need” vaginal prep, Dr. Lew said. “Currently, the standard does not require doing a vaginal prep for any cesarean sections, those in labor or not.”

The researchers have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Vaginal cleansing showed no reduction in morbidity when performed before unscheduled cesarean deliveries, researchers reported at the 2022 Pregnancy Meeting of the Society for Maternal-Fetal Medicine.

Several studies have evaluated vaginal cleansing prior to cesarean delivery, with mixed results. The American College of Obstetricians and Gynecologists recommends clinicians consider cleansing prior to unscheduled cesareans, but that advice appears not to be widely heeded.

The new findings, from what the researchers called the single largest study of vaginal cleansing prior to cesarean delivery in the United States, showed no difference in post-cesarean infections when the vagina was cleansed with povidone-iodine prior to unscheduled cesarean delivery.

“These findings do not support routine vaginal cleansing prior to unscheduled cesarean deliveries,” lead author Lorene Atkins Temming, MD, medical director of labor and delivery at Atrium Health Wake Forest School of Medicine, Charlotte, North Carolina, told this news organization. The research was conducted at and sponsored by Washington University School of Medicine, St. Louis, where Dr. Temming did her fellowship.

Dr. Temming’s group compared vaginal cleansing with povidone-iodine in addition to routine abdominal cleansing to abdominal cleansing alone. Among the primary outcomes of the study was the effect of cleansing on post-cesarean infectious morbidity.

“There is a higher risk of infectious complications after cesarean delivery than other gynecologic surgeries,” Dr. Temming told this news organization. “While the reason for this isn’t entirely clear, it is thought to be because cesareans are often performed after a patient’s cervix is dilated. This dilation can allow normal bacteria that live in the vagina to ascend into the uterus and can increase the risk of infections.”

Patients undergoing cesarean delivery after labor were randomly assigned to undergo preoperative abdominal cleansing only (n = 304) or preoperative abdominal cleansing plus vaginal cleansing with povidone-iodine (n = 304). Women were included in the analysis if they underwent cesareans after regular contractions and any cervical dilation, if their membranes ruptured, or if they had the procedure performed when they were more than 4 cm dilated.

The primary outcome was composite infectious morbidity, a catchall that included surgical-site infection, maternal fever, endometritis, and wound complications within 30 days after cesarean delivery. The secondary outcomes were hospital readmission, visits to the emergency department, and treatment for neonatal sepsis.

The researchers observed no significant difference in the primary composite outcome between the two groups (11.7% vs. 11.7%, P = .98; 95% confidence interval, 0.6-1.5). “Vaginal cleansing appears to be unnecessary when preoperative antibiotics and skin antisepsis are performed,” Dr. Temming said.

Jennifer L. Lew, MD, an ob/gyn at Northwestern Medicine Kishwaukee Hospital in Dekalb, Illinois, said current practice regarding preparation for unscheduled cesarean surgery includes chlorhexidine on the abdomen and povidone-iodine for introducing a Foley catheter into the urethra.

“Many patients may already have a catheter in place due to labor and epidural, so they would not need” vaginal prep, Dr. Lew said. “Currently, the standard does not require doing a vaginal prep for any cesarean sections, those in labor or not.”

The researchers have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Vaginal cleansing showed no reduction in morbidity when performed before unscheduled cesarean deliveries, researchers reported at the 2022 Pregnancy Meeting of the Society for Maternal-Fetal Medicine.

Several studies have evaluated vaginal cleansing prior to cesarean delivery, with mixed results. The American College of Obstetricians and Gynecologists recommends clinicians consider cleansing prior to unscheduled cesareans, but that advice appears not to be widely heeded.

The new findings, from what the researchers called the single largest study of vaginal cleansing prior to cesarean delivery in the United States, showed no difference in post-cesarean infections when the vagina was cleansed with povidone-iodine prior to unscheduled cesarean delivery.

“These findings do not support routine vaginal cleansing prior to unscheduled cesarean deliveries,” lead author Lorene Atkins Temming, MD, medical director of labor and delivery at Atrium Health Wake Forest School of Medicine, Charlotte, North Carolina, told this news organization. The research was conducted at and sponsored by Washington University School of Medicine, St. Louis, where Dr. Temming did her fellowship.

Dr. Temming’s group compared vaginal cleansing with povidone-iodine in addition to routine abdominal cleansing to abdominal cleansing alone. Among the primary outcomes of the study was the effect of cleansing on post-cesarean infectious morbidity.

“There is a higher risk of infectious complications after cesarean delivery than other gynecologic surgeries,” Dr. Temming told this news organization. “While the reason for this isn’t entirely clear, it is thought to be because cesareans are often performed after a patient’s cervix is dilated. This dilation can allow normal bacteria that live in the vagina to ascend into the uterus and can increase the risk of infections.”

Patients undergoing cesarean delivery after labor were randomly assigned to undergo preoperative abdominal cleansing only (n = 304) or preoperative abdominal cleansing plus vaginal cleansing with povidone-iodine (n = 304). Women were included in the analysis if they underwent cesareans after regular contractions and any cervical dilation, if their membranes ruptured, or if they had the procedure performed when they were more than 4 cm dilated.

The primary outcome was composite infectious morbidity, a catchall that included surgical-site infection, maternal fever, endometritis, and wound complications within 30 days after cesarean delivery. The secondary outcomes were hospital readmission, visits to the emergency department, and treatment for neonatal sepsis.

The researchers observed no significant difference in the primary composite outcome between the two groups (11.7% vs. 11.7%, P = .98; 95% confidence interval, 0.6-1.5). “Vaginal cleansing appears to be unnecessary when preoperative antibiotics and skin antisepsis are performed,” Dr. Temming said.

Jennifer L. Lew, MD, an ob/gyn at Northwestern Medicine Kishwaukee Hospital in Dekalb, Illinois, said current practice regarding preparation for unscheduled cesarean surgery includes chlorhexidine on the abdomen and povidone-iodine for introducing a Foley catheter into the urethra.

“Many patients may already have a catheter in place due to labor and epidural, so they would not need” vaginal prep, Dr. Lew said. “Currently, the standard does not require doing a vaginal prep for any cesarean sections, those in labor or not.”

The researchers have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

It seems obvious that increased use of mosquito bed nets in sub-Saharan Africa would decrease the incidence of malaria, but a lingering question remained: Would controlling malaria in children under 5 years of age shift deaths to older children by delaying functional immunity?  A new report in the New England Journal of Medicine seems to have laid that concern to rest.

Malaria from Plasmodium falciparum infection exacts a significant toll in sub-Saharan Africa. According to the World Health Organization, there were about 228 million cases and 602,000 deaths from malaria in 2020 alone. About 80% of those deaths were in children less than 5 years old. In some areas, as many as 5% of children die from malaria by age 5.

Efforts to reduce the burden of malaria have been ongoing for decades. In the 1990s, insecticide-treated nets were shown to reduce illness and deaths from malaria in children.

As a result, the use of bed nets has grown significantly. In 2000, only 5% of households in sub-Saharan Africa had a net in the house. By 2020, that number had risen to 65%. From 2004 to 2019 about 1.9 billion nets were distributed in this region. The nets are estimated to have prevented more than 663 million malaria cases between 2000 and 2015.

As described in the NEJM report, public health researchers conducted a 22-year prospective longitudinal cohort study in rural southern Tanzania following 6,706 children born between 1998 and 2000. Initially, home visits were made every 4 months from May 1998 to April 2003. Remarkably, in 2019, they were able to verify the status of fully 89% of those people by reaching out to families and community/village leaders.

Günther Fink, PhD, associate professor of epidemiology and household economics, University of Basel (Switzerland), explained the approach and primary findings to this news organization. The analysis looked at three main groups – children whose parents said they always slept under treated nets, those who slept protected most of the time, and those who spent less than half the time under bed nets. The hazard ratio for death was 0.57 (95% confidence interval, 0.45-0.72) for the first two groups, compared with the least protected. The corresponding hazard ratio between age 5 and adulthood was 0.93 (95% CI, 0.58-1.49).

The findings confirmed what they had suspected. Dr. Fink summarized simply, “If you always slept under a net, you did much better than if you never slept under the net. If you slept [under a net] more than half of the time, it was much better than if you slept [under a net] less than half the time.” So the more time children slept under bed nets, the less likely they were to acquire malaria. Dr. Fink stressed that the findings showing protective efficacy persisted into adulthood. “It seems just having a healthier early life actually makes you more resilient against other future infections.”

One of the theoretical concerns was that using nets would delay developing functional immunity and that there might be an increase in mortality seen later. This study showed that did not happen.

An accompanying commentary noted that there was some potential that families receiving nets were better off than those that didn’t but concluded that such confounding had been accounted for in other analyses.

Mark Wilson, ScD, professor emeritus of epidemiology, University of Michigan, Ann Arbor, concurred. He told this news organization that the study was “very well designed,” and the researchers “did a fantastic job” in tracking patients 20 years later.

“This is astounding!” he added. “It’s very rare to find this amount of follow-up.”

Dr. Fink’s conclusion? “Bed nets protect you in the short run, and being protected in the short run is also beneficial in the long run. There is no evidence that protecting kids in early childhood is weakening them in any way. So we should keep doing this.”

Dr. Fink and Dr. Wilson report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

It seems obvious that increased use of mosquito bed nets in sub-Saharan Africa would decrease the incidence of malaria, but a lingering question remained: Would controlling malaria in children under 5 years of age shift deaths to older children by delaying functional immunity?  A new report in the New England Journal of Medicine seems to have laid that concern to rest.

Malaria from Plasmodium falciparum infection exacts a significant toll in sub-Saharan Africa. According to the World Health Organization, there were about 228 million cases and 602,000 deaths from malaria in 2020 alone. About 80% of those deaths were in children less than 5 years old. In some areas, as many as 5% of children die from malaria by age 5.

Efforts to reduce the burden of malaria have been ongoing for decades. In the 1990s, insecticide-treated nets were shown to reduce illness and deaths from malaria in children.

As a result, the use of bed nets has grown significantly. In 2000, only 5% of households in sub-Saharan Africa had a net in the house. By 2020, that number had risen to 65%. From 2004 to 2019 about 1.9 billion nets were distributed in this region. The nets are estimated to have prevented more than 663 million malaria cases between 2000 and 2015.

As described in the NEJM report, public health researchers conducted a 22-year prospective longitudinal cohort study in rural southern Tanzania following 6,706 children born between 1998 and 2000. Initially, home visits were made every 4 months from May 1998 to April 2003. Remarkably, in 2019, they were able to verify the status of fully 89% of those people by reaching out to families and community/village leaders.

Günther Fink, PhD, associate professor of epidemiology and household economics, University of Basel (Switzerland), explained the approach and primary findings to this news organization. The analysis looked at three main groups – children whose parents said they always slept under treated nets, those who slept protected most of the time, and those who spent less than half the time under bed nets. The hazard ratio for death was 0.57 (95% confidence interval, 0.45-0.72) for the first two groups, compared with the least protected. The corresponding hazard ratio between age 5 and adulthood was 0.93 (95% CI, 0.58-1.49).

The findings confirmed what they had suspected. Dr. Fink summarized simply, “If you always slept under a net, you did much better than if you never slept under the net. If you slept [under a net] more than half of the time, it was much better than if you slept [under a net] less than half the time.” So the more time children slept under bed nets, the less likely they were to acquire malaria. Dr. Fink stressed that the findings showing protective efficacy persisted into adulthood. “It seems just having a healthier early life actually makes you more resilient against other future infections.”

One of the theoretical concerns was that using nets would delay developing functional immunity and that there might be an increase in mortality seen later. This study showed that did not happen.

An accompanying commentary noted that there was some potential that families receiving nets were better off than those that didn’t but concluded that such confounding had been accounted for in other analyses.

Mark Wilson, ScD, professor emeritus of epidemiology, University of Michigan, Ann Arbor, concurred. He told this news organization that the study was “very well designed,” and the researchers “did a fantastic job” in tracking patients 20 years later.

“This is astounding!” he added. “It’s very rare to find this amount of follow-up.”

Dr. Fink’s conclusion? “Bed nets protect you in the short run, and being protected in the short run is also beneficial in the long run. There is no evidence that protecting kids in early childhood is weakening them in any way. So we should keep doing this.”

Dr. Fink and Dr. Wilson report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

It seems obvious that increased use of mosquito bed nets in sub-Saharan Africa would decrease the incidence of malaria, but a lingering question remained: Would controlling malaria in children under 5 years of age shift deaths to older children by delaying functional immunity?  A new report in the New England Journal of Medicine seems to have laid that concern to rest.

Malaria from Plasmodium falciparum infection exacts a significant toll in sub-Saharan Africa. According to the World Health Organization, there were about 228 million cases and 602,000 deaths from malaria in 2020 alone. About 80% of those deaths were in children less than 5 years old. In some areas, as many as 5% of children die from malaria by age 5.

Efforts to reduce the burden of malaria have been ongoing for decades. In the 1990s, insecticide-treated nets were shown to reduce illness and deaths from malaria in children.

As a result, the use of bed nets has grown significantly. In 2000, only 5% of households in sub-Saharan Africa had a net in the house. By 2020, that number had risen to 65%. From 2004 to 2019 about 1.9 billion nets were distributed in this region. The nets are estimated to have prevented more than 663 million malaria cases between 2000 and 2015.

As described in the NEJM report, public health researchers conducted a 22-year prospective longitudinal cohort study in rural southern Tanzania following 6,706 children born between 1998 and 2000. Initially, home visits were made every 4 months from May 1998 to April 2003. Remarkably, in 2019, they were able to verify the status of fully 89% of those people by reaching out to families and community/village leaders.

Günther Fink, PhD, associate professor of epidemiology and household economics, University of Basel (Switzerland), explained the approach and primary findings to this news organization. The analysis looked at three main groups – children whose parents said they always slept under treated nets, those who slept protected most of the time, and those who spent less than half the time under bed nets. The hazard ratio for death was 0.57 (95% confidence interval, 0.45-0.72) for the first two groups, compared with the least protected. The corresponding hazard ratio between age 5 and adulthood was 0.93 (95% CI, 0.58-1.49).

The findings confirmed what they had suspected. Dr. Fink summarized simply, “If you always slept under a net, you did much better than if you never slept under the net. If you slept [under a net] more than half of the time, it was much better than if you slept [under a net] less than half the time.” So the more time children slept under bed nets, the less likely they were to acquire malaria. Dr. Fink stressed that the findings showing protective efficacy persisted into adulthood. “It seems just having a healthier early life actually makes you more resilient against other future infections.”

One of the theoretical concerns was that using nets would delay developing functional immunity and that there might be an increase in mortality seen later. This study showed that did not happen.

An accompanying commentary noted that there was some potential that families receiving nets were better off than those that didn’t but concluded that such confounding had been accounted for in other analyses.

Mark Wilson, ScD, professor emeritus of epidemiology, University of Michigan, Ann Arbor, concurred. He told this news organization that the study was “very well designed,” and the researchers “did a fantastic job” in tracking patients 20 years later.

“This is astounding!” he added. “It’s very rare to find this amount of follow-up.”

Dr. Fink’s conclusion? “Bed nets protect you in the short run, and being protected in the short run is also beneficial in the long run. There is no evidence that protecting kids in early childhood is weakening them in any way. So we should keep doing this.”

Dr. Fink and Dr. Wilson report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved rilpivirine and cabotegravir (Cabenuva) to 2-month dosing for adults living with HIV-1 infection.

Cabenuva was first approved by the FDA in January 2021 to be administered once monthly to treat HIV-1 infection in virologically suppressed adults. The medication was the first injectable complete antiretroviral regimen approved by the FDA.

Cabenuva can replace a current treatment in virologically suppressed adults on a stable antiretroviral regimen with no history of treatment failure and no known or suspected resistance to rilpivirine and cabotegravir, the Janssen Pharmaceutical Companies of Johnson & Johnson said in a press release. Janssen and ViiV Healthcare codeveloped the injectable antiretroviral medication Cabenuva.

The expanded label approval “marks an important step forward in advancing the treatment landscape for people living with HIV,” said Candice Long, the president of infectious diseases and vaccines at Janssen Therapeutics, in a Feb. 1 press release. “With this milestone, adults living with HIV have a treatment option that further reduces the frequency of medication.”

This expanded approval was based on global clinical trial of 1,045 adults with HIV-1, which found Cabenuva administered every 8 weeks (3 mL dose of both cabotegravir and rilpivirine) to be noninferior to the 4-week regimen (2 mL dose of both medicines). At week 48 of the trial, the proportion of participants with viral loads above 50 copies per milliliter was 1.7% in the 2-month arm and 1.0% in the 1-month arm. The study found that rates of virological suppression were similar for both the 1-month and 2-month regimens (93.5% and 94.3%, respectively).

The most common side effects were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash. Adverse reactions reported in individuals receiving the regimen every 2 months or once monthly were similar. Cabenuva is contraindicated for patients with a hypersensitivity reaction to cabotegravir or rilpivirine or for those receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, St. John’s wort, and more than one dose of systemic dexamethasone.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved rilpivirine and cabotegravir (Cabenuva) to 2-month dosing for adults living with HIV-1 infection.

Cabenuva was first approved by the FDA in January 2021 to be administered once monthly to treat HIV-1 infection in virologically suppressed adults. The medication was the first injectable complete antiretroviral regimen approved by the FDA.

Cabenuva can replace a current treatment in virologically suppressed adults on a stable antiretroviral regimen with no history of treatment failure and no known or suspected resistance to rilpivirine and cabotegravir, the Janssen Pharmaceutical Companies of Johnson & Johnson said in a press release. Janssen and ViiV Healthcare codeveloped the injectable antiretroviral medication Cabenuva.

The expanded label approval “marks an important step forward in advancing the treatment landscape for people living with HIV,” said Candice Long, the president of infectious diseases and vaccines at Janssen Therapeutics, in a Feb. 1 press release. “With this milestone, adults living with HIV have a treatment option that further reduces the frequency of medication.”

This expanded approval was based on global clinical trial of 1,045 adults with HIV-1, which found Cabenuva administered every 8 weeks (3 mL dose of both cabotegravir and rilpivirine) to be noninferior to the 4-week regimen (2 mL dose of both medicines). At week 48 of the trial, the proportion of participants with viral loads above 50 copies per milliliter was 1.7% in the 2-month arm and 1.0% in the 1-month arm. The study found that rates of virological suppression were similar for both the 1-month and 2-month regimens (93.5% and 94.3%, respectively).

The most common side effects were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash. Adverse reactions reported in individuals receiving the regimen every 2 months or once monthly were similar. Cabenuva is contraindicated for patients with a hypersensitivity reaction to cabotegravir or rilpivirine or for those receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, St. John’s wort, and more than one dose of systemic dexamethasone.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved rilpivirine and cabotegravir (Cabenuva) to 2-month dosing for adults living with HIV-1 infection.

Cabenuva was first approved by the FDA in January 2021 to be administered once monthly to treat HIV-1 infection in virologically suppressed adults. The medication was the first injectable complete antiretroviral regimen approved by the FDA.

Cabenuva can replace a current treatment in virologically suppressed adults on a stable antiretroviral regimen with no history of treatment failure and no known or suspected resistance to rilpivirine and cabotegravir, the Janssen Pharmaceutical Companies of Johnson & Johnson said in a press release. Janssen and ViiV Healthcare codeveloped the injectable antiretroviral medication Cabenuva.

The expanded label approval “marks an important step forward in advancing the treatment landscape for people living with HIV,” said Candice Long, the president of infectious diseases and vaccines at Janssen Therapeutics, in a Feb. 1 press release. “With this milestone, adults living with HIV have a treatment option that further reduces the frequency of medication.”

This expanded approval was based on global clinical trial of 1,045 adults with HIV-1, which found Cabenuva administered every 8 weeks (3 mL dose of both cabotegravir and rilpivirine) to be noninferior to the 4-week regimen (2 mL dose of both medicines). At week 48 of the trial, the proportion of participants with viral loads above 50 copies per milliliter was 1.7% in the 2-month arm and 1.0% in the 1-month arm. The study found that rates of virological suppression were similar for both the 1-month and 2-month regimens (93.5% and 94.3%, respectively).

The most common side effects were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash. Adverse reactions reported in individuals receiving the regimen every 2 months or once monthly were similar. Cabenuva is contraindicated for patients with a hypersensitivity reaction to cabotegravir or rilpivirine or for those receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, St. John’s wort, and more than one dose of systemic dexamethasone.

A version of this article first appeared on Medscape.com.

As rheumatologists contend with vaccine hesitancy among certain subsets of patients, the American College of Rheumatology has released updated clinical guidelines on COVID-19 vaccination for patients with rheumatic and musculoskeletal diseases (RMDs), including new recommendations on supplemental and booster doses.

The revised guidance from this fifth version of the ACR guidelines includes strongly recommending that all RMD patients receive a booster after their primary vaccine series, regardless of whether they have been naturally infected with COVID-19. In addition, they strongly recommend third supplemental doses for patients with autoimmune inflammatory rheumatic diseases (AIIRDs) who likely mounted an inadequate vaccine response, which would then be followed by a fourth booster dose as advised by the Centers for Disease Control and Prevention for immunocompromised individuals.

South_agency/Getty Images

Other recommendations include pre-exposure prophylaxis monoclonal antibody treatment for high-risk AIIRD patients, defined as those with moderate to severely compromised immune systems who may not mount an adequate immune response to COVID-19 vaccination, when it is available and authorized for emergency use by the Food and Drug Administration, as well as monoclonal antibody therapy for postexposure prophylaxis of asymptomatic, recently exposed high-risk AIIRD patients or as treatment for newly symptomatic, high-risk AIIRD patients. The ACR guidance notes that, currently, neither the monoclonal antibodies bamlanivimab and etesevimab (administered together) nor casirivimab and imdevimab (REGEN-COV), are licensed or available under an emergency use authorization given their lack of activity against the Omicron variant, the dominant strain of SARS-CoV-2 circulating in the United States.

Finally, the guidance clarified that the timing of intravenous immunoglobulin doses does not need to be modified around the administration of COVID vaccine doses, based on moderate consensus among task force members.

Vaccine hesitancy in community rheumatology practices

The revised guidelines were released just as Arthritis & Rheumatology published a new study that assessed vaccine hesitancy among rheumatology patients on immunomodulatory therapies. A three-item electronic survey was conducted at 101 offices within a community practice–based rheumatology research network and ultimately collected responses from 58,529 patients, 20,987 of whom had an AIIRD and were receiving targeted therapies like biologics or Janus kinase inhibitors.

Of the total respondents, 77% (n = 43,675) had been vaccinated, 16.9% were not vaccinated and did not plan to be, and 6.1% were not vaccinated but planned to be. However, AIIRD patients were 16% less likely to be vaccinated, compared with the other patients, such as those with osteoarthritis or osteoporosis who were not receiving disease-modifying antirheumatic drugs (76.9% vs. 87%; odds ratio, 0.84; 95% confidence interval, 0.77-0.92; P < .001). Multivariable analysis also found that older patients (OR, 1.49 per 10 years) and Asians (OR, 2.42; 95% CI, 1.77-3.33) were more likely to be vaccinated.

Courtesy UAB Photo

“Rheumatologists need to be asking their patients more than just: ‘Are you vaccinated?’ ” Jeffrey Curtis, MD, MPH, head of the ACR COVID-19 vaccine task force and a coauthor of the vaccine hesitancy study, said in an interview. “A year ago, that was a fine approach, but now they need to be asking whether you’ve been vaccinated, and with what, and how many times, and how recently. There are a whole lot of subtleties there; ‘vaccinated: yes or no’ is just the tip of the iceberg.”

His research into the vaccine hesitant includes recent anecdotal data from thousands of patients treated in local rheumatology community practices, many of whom cited long-term safety data and potential side effects as reasons why they were unwilling to get vaccinated. But despite their on-paper responses, he cautioned rheumatologists to think critically when determining which patients may truly be open to vaccination.

“If you’re designing strategies to affect vaccine hesitancy, you may be wasting your time with some people,” said Dr. Curtis, professor of medicine at the University of Alabama at Birmingham. “A critical need is to figure out who are the patients who may be amendable to more information or an intervention or a little bit more time and care, and who are the people where you know, this is a lost cause: You don’t get a flu shot, you haven’t been vaccinated for shingles, [and] you’re not going to get this one either.

“In terms of a research agenda, how do we develop efficient, simple, short screening tools?” he added. “Something with a few helpful questions, on a patient portal or an iPad, that will do a good job identifying your patients at risk who haven’t had vaccination but that you might be able to spend time with, intervene, and actually change their mind. If you spend gobs of time with everyone, you’ll help some people, but clinicians don’t have an infinite amount of time.”

One of the authors of the vaccine hesitancy study acknowledged being employed by the rheumatology research network that hosted the survey. Several others, including Dr. Curtis, reported receiving grants and consulting fees from various pharmaceutical companies.

As rheumatologists contend with vaccine hesitancy among certain subsets of patients, the American College of Rheumatology has released updated clinical guidelines on COVID-19 vaccination for patients with rheumatic and musculoskeletal diseases (RMDs), including new recommendations on supplemental and booster doses.

The revised guidance from this fifth version of the ACR guidelines includes strongly recommending that all RMD patients receive a booster after their primary vaccine series, regardless of whether they have been naturally infected with COVID-19. In addition, they strongly recommend third supplemental doses for patients with autoimmune inflammatory rheumatic diseases (AIIRDs) who likely mounted an inadequate vaccine response, which would then be followed by a fourth booster dose as advised by the Centers for Disease Control and Prevention for immunocompromised individuals.

South_agency/Getty Images

Other recommendations include pre-exposure prophylaxis monoclonal antibody treatment for high-risk AIIRD patients, defined as those with moderate to severely compromised immune systems who may not mount an adequate immune response to COVID-19 vaccination, when it is available and authorized for emergency use by the Food and Drug Administration, as well as monoclonal antibody therapy for postexposure prophylaxis of asymptomatic, recently exposed high-risk AIIRD patients or as treatment for newly symptomatic, high-risk AIIRD patients. The ACR guidance notes that, currently, neither the monoclonal antibodies bamlanivimab and etesevimab (administered together) nor casirivimab and imdevimab (REGEN-COV), are licensed or available under an emergency use authorization given their lack of activity against the Omicron variant, the dominant strain of SARS-CoV-2 circulating in the United States.

Finally, the guidance clarified that the timing of intravenous immunoglobulin doses does not need to be modified around the administration of COVID vaccine doses, based on moderate consensus among task force members.

Vaccine hesitancy in community rheumatology practices

The revised guidelines were released just as Arthritis & Rheumatology published a new study that assessed vaccine hesitancy among rheumatology patients on immunomodulatory therapies. A three-item electronic survey was conducted at 101 offices within a community practice–based rheumatology research network and ultimately collected responses from 58,529 patients, 20,987 of whom had an AIIRD and were receiving targeted therapies like biologics or Janus kinase inhibitors.

Of the total respondents, 77% (n = 43,675) had been vaccinated, 16.9% were not vaccinated and did not plan to be, and 6.1% were not vaccinated but planned to be. However, AIIRD patients were 16% less likely to be vaccinated, compared with the other patients, such as those with osteoarthritis or osteoporosis who were not receiving disease-modifying antirheumatic drugs (76.9% vs. 87%; odds ratio, 0.84; 95% confidence interval, 0.77-0.92; P < .001). Multivariable analysis also found that older patients (OR, 1.49 per 10 years) and Asians (OR, 2.42; 95% CI, 1.77-3.33) were more likely to be vaccinated.

Courtesy UAB Photo

“Rheumatologists need to be asking their patients more than just: ‘Are you vaccinated?’ ” Jeffrey Curtis, MD, MPH, head of the ACR COVID-19 vaccine task force and a coauthor of the vaccine hesitancy study, said in an interview. “A year ago, that was a fine approach, but now they need to be asking whether you’ve been vaccinated, and with what, and how many times, and how recently. There are a whole lot of subtleties there; ‘vaccinated: yes or no’ is just the tip of the iceberg.”

His research into the vaccine hesitant includes recent anecdotal data from thousands of patients treated in local rheumatology community practices, many of whom cited long-term safety data and potential side effects as reasons why they were unwilling to get vaccinated. But despite their on-paper responses, he cautioned rheumatologists to think critically when determining which patients may truly be open to vaccination.

“If you’re designing strategies to affect vaccine hesitancy, you may be wasting your time with some people,” said Dr. Curtis, professor of medicine at the University of Alabama at Birmingham. “A critical need is to figure out who are the patients who may be amendable to more information or an intervention or a little bit more time and care, and who are the people where you know, this is a lost cause: You don’t get a flu shot, you haven’t been vaccinated for shingles, [and] you’re not going to get this one either.

“In terms of a research agenda, how do we develop efficient, simple, short screening tools?” he added. “Something with a few helpful questions, on a patient portal or an iPad, that will do a good job identifying your patients at risk who haven’t had vaccination but that you might be able to spend time with, intervene, and actually change their mind. If you spend gobs of time with everyone, you’ll help some people, but clinicians don’t have an infinite amount of time.”

One of the authors of the vaccine hesitancy study acknowledged being employed by the rheumatology research network that hosted the survey. Several others, including Dr. Curtis, reported receiving grants and consulting fees from various pharmaceutical companies.

As rheumatologists contend with vaccine hesitancy among certain subsets of patients, the American College of Rheumatology has released updated clinical guidelines on COVID-19 vaccination for patients with rheumatic and musculoskeletal diseases (RMDs), including new recommendations on supplemental and booster doses.

The revised guidance from this fifth version of the ACR guidelines includes strongly recommending that all RMD patients receive a booster after their primary vaccine series, regardless of whether they have been naturally infected with COVID-19. In addition, they strongly recommend third supplemental doses for patients with autoimmune inflammatory rheumatic diseases (AIIRDs) who likely mounted an inadequate vaccine response, which would then be followed by a fourth booster dose as advised by the Centers for Disease Control and Prevention for immunocompromised individuals.

South_agency/Getty Images

Other recommendations include pre-exposure prophylaxis monoclonal antibody treatment for high-risk AIIRD patients, defined as those with moderate to severely compromised immune systems who may not mount an adequate immune response to COVID-19 vaccination, when it is available and authorized for emergency use by the Food and Drug Administration, as well as monoclonal antibody therapy for postexposure prophylaxis of asymptomatic, recently exposed high-risk AIIRD patients or as treatment for newly symptomatic, high-risk AIIRD patients. The ACR guidance notes that, currently, neither the monoclonal antibodies bamlanivimab and etesevimab (administered together) nor casirivimab and imdevimab (REGEN-COV), are licensed or available under an emergency use authorization given their lack of activity against the Omicron variant, the dominant strain of SARS-CoV-2 circulating in the United States.

Finally, the guidance clarified that the timing of intravenous immunoglobulin doses does not need to be modified around the administration of COVID vaccine doses, based on moderate consensus among task force members.

Vaccine hesitancy in community rheumatology practices

The revised guidelines were released just as Arthritis & Rheumatology published a new study that assessed vaccine hesitancy among rheumatology patients on immunomodulatory therapies. A three-item electronic survey was conducted at 101 offices within a community practice–based rheumatology research network and ultimately collected responses from 58,529 patients, 20,987 of whom had an AIIRD and were receiving targeted therapies like biologics or Janus kinase inhibitors.

Of the total respondents, 77% (n = 43,675) had been vaccinated, 16.9% were not vaccinated and did not plan to be, and 6.1% were not vaccinated but planned to be. However, AIIRD patients were 16% less likely to be vaccinated, compared with the other patients, such as those with osteoarthritis or osteoporosis who were not receiving disease-modifying antirheumatic drugs (76.9% vs. 87%; odds ratio, 0.84; 95% confidence interval, 0.77-0.92; P < .001). Multivariable analysis also found that older patients (OR, 1.49 per 10 years) and Asians (OR, 2.42; 95% CI, 1.77-3.33) were more likely to be vaccinated.

Courtesy UAB Photo

“Rheumatologists need to be asking their patients more than just: ‘Are you vaccinated?’ ” Jeffrey Curtis, MD, MPH, head of the ACR COVID-19 vaccine task force and a coauthor of the vaccine hesitancy study, said in an interview. “A year ago, that was a fine approach, but now they need to be asking whether you’ve been vaccinated, and with what, and how many times, and how recently. There are a whole lot of subtleties there; ‘vaccinated: yes or no’ is just the tip of the iceberg.”

His research into the vaccine hesitant includes recent anecdotal data from thousands of patients treated in local rheumatology community practices, many of whom cited long-term safety data and potential side effects as reasons why they were unwilling to get vaccinated. But despite their on-paper responses, he cautioned rheumatologists to think critically when determining which patients may truly be open to vaccination.

“If you’re designing strategies to affect vaccine hesitancy, you may be wasting your time with some people,” said Dr. Curtis, professor of medicine at the University of Alabama at Birmingham. “A critical need is to figure out who are the patients who may be amendable to more information or an intervention or a little bit more time and care, and who are the people where you know, this is a lost cause: You don’t get a flu shot, you haven’t been vaccinated for shingles, [and] you’re not going to get this one either.

“In terms of a research agenda, how do we develop efficient, simple, short screening tools?” he added. “Something with a few helpful questions, on a patient portal or an iPad, that will do a good job identifying your patients at risk who haven’t had vaccination but that you might be able to spend time with, intervene, and actually change their mind. If you spend gobs of time with everyone, you’ll help some people, but clinicians don’t have an infinite amount of time.”

One of the authors of the vaccine hesitancy study acknowledged being employed by the rheumatology research network that hosted the survey. Several others, including Dr. Curtis, reported receiving grants and consulting fees from various pharmaceutical companies.

It is a great mystery of infectious disease: Why are some people seemingly unaffected by illness that harms others? During the COVID-19 pandemic, we’ve seen this play out time and time again when whole families get sick except for one or two fortunate family members. And at so-called superspreader events that infect many, a lucky few typically walk away with their health intact. Did the virus never enter their bodies? Or do some people have natural resistance to pathogens they’ve never been exposed to before encoded in their genes?

Resistance to infectious disease is much more than a scientific curiosity and studying how it works can be a path to curb future outbreaks.

“In the event that we could identify what makes some people resistant, that immediately opens avenues for therapeutics that we could apply in all those other people who do suffer from the disease,” says András Spaan, MD, a microbiologist at Rockefeller University in New York.

Dr. Spaan is part of an international effort to identify genetic variations that spare people from becoming infected with SARS-CoV-2, the virus that causes COVID-19.

There’s far more research on what drives the tendency to get infectious diseases than on resistance to them. But a few researchers are investigating resistance to some of the world’s most common and deadly infectious diseases, and in a few cases, they’ve already translated these insights into treatments.

Perhaps the strongest example of how odd genes of just a few people can inspire treatments to help many comes from research on the human immunodeficiency virus (HIV), the virus that causes acquired immune deficiency syndrome (AIDS).
 

A genetic quirk

In the mid-1990s, several groups of researchers independently identified a mutation in a gene called CCR5 linked to resistance to HIV infection.

The gene encodes a protein on the surface of some white blood cells that helps set up the movement of other immune cells to fight infections. HIV, meanwhile, uses the CCR5 protein to help it enter the white blood cells that it infects.

The mutation, known as delta 32, results in a shorter than usual protein that doesn’t reach the surface of the cell. People who carry two copies of the delta 32 form of CCR5 do not have any CCR5 protein on the outside of their white blood cells.

Researchers, led by molecular immunologist Philip Murphy, MD, at the National Institute of Allergy and Infectious Diseases in Bethesda, Md, showed in 1997 that people with two copies of the mutation were unusually common among a group of men who were at especially high risk of HIV exposure, but had never contracted the virus. And out of more than 700 HIV-positive people, none carried two copies of CCR5 delta 32.

Pharmaceutical companies used these insights to develop drugs to block CCR5 and delay the development of AIDS. For instance, the drug maraviroc, marketed by Pfizer, was approved for use in HIV-positive people in 2007.

Only a few examples of this kind of inborn, genetically determined complete resistance to infection have ever been heard of. All of them involve cell-surface molecules that are believed to help a virus or other pathogen gain entry to the cell.
 

Locking out illness

“The first step for any intracellular pathogen is getting inside the cell. And if you’re missing the doorway, then the virus can’t accomplish the first step in its life cycle,” Dr. Murphy says. “Getting inside is fundamental.”

Changes in cell-surface molecules can also make someone more likely to have an infection or severe disease. One such group of cell-surface molecules that have been linked to both increasing and decreasing the risk of various infections are histo-blood group antigens. The most familiar members of this group are the molecules that define blood types A, B, and O.

Scientists have also identified one example of total resistance to infection involving these molecules. In 2003, researchers showed that people who lack a functional copy of a gene known as FUT2 cannot be infected with Norwalk virus, one of more than 30 viruses in the norovirus family that cause illness in the digestive tract.

The gene FUT2 encodes an enzyme that determines whether or not blood group antigens are found in a person’s saliva and other body fluids as well as on their red blood cells.

“It didn’t matter how many virus particles we challenged an individual with, if they did not have that first enzyme, they did not get infected,” says researcher Lisa Lindesmith, a virologist at the University of North Carolina in Chapel Hill.
 

No norovirus

Norwalk is a relatively rare type of norovirus. But FUT2 deficiency also provides some protection against the most common strains of norovirus, known as GII.4, which have periodically swept across the world over the past quarter-century. These illnesses take an especially heavy toll on children in the developing world, causing malnutrition and contributing to infant and child deaths.

But progress in translating these insights about genetic resistance into drugs or other things that could reduce the burden of noroviruses has been slow.

“The biggest barrier here is lack of ability to study the virus outside of humans,” Lindesmith says.

Noroviruses are very difficult to grow in the lab, “and there’s no small animal model of gastrointestinal illness caused by the viruses.”

We are clearly making giant strides in improving those skills,” says Lindesmith. “But we are just not quite there yet.”

In the years before COVID-19 emerged, tuberculosis was responsible for the largest number of annual worldwide deaths from an infectious disease. It’s a lung disease caused by the bacterium Mycobacterium tuberculosis, and it has been a pandemic for thousands of years.

Some 85%-95% of people with intact immune systems who are infected with TB control the infection and never get active lung disease. And some people who have intense, continuing exposure to the bacterium, which is spread through droplets and aerosols from people with active lung disease, apparently never become infected at all.
 

Thwarting uberculosis

Understanding the ways of these different forms of resistance could help in the search for vaccines, treatments, and other ways to fight tuberculosis, says Elouise Kroon, MD, a graduate student at Stellenbosch University in Cape Town, South Africa.

“What makes it particularly hard to study is the fact that there is no gold standard to measure infection,” she says. “So, what we do is infer infection from two different types of tests” -- a skin test and a blood test that measure different kinds of immune response to molecules from the bacterium.

Dr. Kroon and other researchers have studied resistance to infection by following people living in the same household as those with active lung disease or people who live and work in crowded conditions in high-risk communities. But not all such studies have used the same definition of so-called resisters, documented exposure in the same way, or followed up to ensure that people continue to test negative over the long term.

The best clue that has emerged from studies so far links resistance to infection to certain variations in immune molecules known as HLA class II antigens, says Marlo Möller, PhD, a professor in the TB Host Genetics Research Group at Stellenbosch University.

“That always seems to pop up everywhere. But the rest is not so obvious,” she says. “A lot of the studies don’t find the same thing. It’s different in different populations,” which may be a result of the long evolutionary history between tuberculosis and humans, as well as the fact that different strains of the bacterium are prevalent in different parts of the world.

COVID-19 is a much newer infectious disease, but teasing out how it contributes to both severe illness and resistance to infection is still a major task.
 

Overcoming COVID

Early in the pandemic, research by the COVID Human Genetic Effort, the international consortium that Dr. Spaan is part of, linked severe COVID-19 pneumonia to the lack of immune molecules known as type I interferons and to antibodies produced by the body that destroy these molecules. Together, these mechanisms explain about one-fifth of severe COVID-19 cases, the researchers reported in 2021.

A few studies by other groups have explored resistance to COVID-19 infection, suggesting that reduced risk of contracting the virus is tied to certain blood group factors. People with Type O blood appear to be at slightly reduced risk of infection, for example.

But the studies done so far are designed to find common genetic variations, which generally have a small effect on resistance. Now, genetic researchers are launching an effort to identify genetic resistance factors with a big effect, even if they are vanishingly rare.

The group is recruiting people who did not become infected with COVID-19 despite heavy exposure, such as those living in households where all the other members got sick or people who were exposed to a superspreader event but did not become ill. As with tuberculosis, being certain that someone has not been infected with the virus can be tricky, but the team is using several blood tests to home in on the people most likely to have escaped infection.

They plan to sequence the genomes of these people to identify things that strongly affect infection risk, then do more laboratory studies to try to tease out the means of resistance.

Their work is inspired by earlier efforts to uncover inborn resistance to infections, Dr. Spaan says. Despite the lack of known examples of such resistance, he is optimistic about the possibilities. Those earlier efforts took place in “a different epoch,” before there were rapid sequencing technologies, Dr. Spaan says.

“Now we have modern technologies to do this more systematically.”

The emergence of viral variants such as the Delta and Omicron COVID strains raises the stakes of the work, he continues.

“The need to unravel these inborn mechanisms of resistance to COVID has become even more important because of these new variants and the anticipation that we will have COVID with us for years.”

A version of this article first appeared on WebMD.com.

It is a great mystery of infectious disease: Why are some people seemingly unaffected by illness that harms others? During the COVID-19 pandemic, we’ve seen this play out time and time again when whole families get sick except for one or two fortunate family members. And at so-called superspreader events that infect many, a lucky few typically walk away with their health intact. Did the virus never enter their bodies? Or do some people have natural resistance to pathogens they’ve never been exposed to before encoded in their genes?

Resistance to infectious disease is much more than a scientific curiosity and studying how it works can be a path to curb future outbreaks.

“In the event that we could identify what makes some people resistant, that immediately opens avenues for therapeutics that we could apply in all those other people who do suffer from the disease,” says András Spaan, MD, a microbiologist at Rockefeller University in New York.

Dr. Spaan is part of an international effort to identify genetic variations that spare people from becoming infected with SARS-CoV-2, the virus that causes COVID-19.

There’s far more research on what drives the tendency to get infectious diseases than on resistance to them. But a few researchers are investigating resistance to some of the world’s most common and deadly infectious diseases, and in a few cases, they’ve already translated these insights into treatments.

Perhaps the strongest example of how odd genes of just a few people can inspire treatments to help many comes from research on the human immunodeficiency virus (HIV), the virus that causes acquired immune deficiency syndrome (AIDS).
 

A genetic quirk

In the mid-1990s, several groups of researchers independently identified a mutation in a gene called CCR5 linked to resistance to HIV infection.

The gene encodes a protein on the surface of some white blood cells that helps set up the movement of other immune cells to fight infections. HIV, meanwhile, uses the CCR5 protein to help it enter the white blood cells that it infects.

The mutation, known as delta 32, results in a shorter than usual protein that doesn’t reach the surface of the cell. People who carry two copies of the delta 32 form of CCR5 do not have any CCR5 protein on the outside of their white blood cells.

Researchers, led by molecular immunologist Philip Murphy, MD, at the National Institute of Allergy and Infectious Diseases in Bethesda, Md, showed in 1997 that people with two copies of the mutation were unusually common among a group of men who were at especially high risk of HIV exposure, but had never contracted the virus. And out of more than 700 HIV-positive people, none carried two copies of CCR5 delta 32.

Pharmaceutical companies used these insights to develop drugs to block CCR5 and delay the development of AIDS. For instance, the drug maraviroc, marketed by Pfizer, was approved for use in HIV-positive people in 2007.

Only a few examples of this kind of inborn, genetically determined complete resistance to infection have ever been heard of. All of them involve cell-surface molecules that are believed to help a virus or other pathogen gain entry to the cell.
 

Locking out illness

“The first step for any intracellular pathogen is getting inside the cell. And if you’re missing the doorway, then the virus can’t accomplish the first step in its life cycle,” Dr. Murphy says. “Getting inside is fundamental.”

Changes in cell-surface molecules can also make someone more likely to have an infection or severe disease. One such group of cell-surface molecules that have been linked to both increasing and decreasing the risk of various infections are histo-blood group antigens. The most familiar members of this group are the molecules that define blood types A, B, and O.

Scientists have also identified one example of total resistance to infection involving these molecules. In 2003, researchers showed that people who lack a functional copy of a gene known as FUT2 cannot be infected with Norwalk virus, one of more than 30 viruses in the norovirus family that cause illness in the digestive tract.

The gene FUT2 encodes an enzyme that determines whether or not blood group antigens are found in a person’s saliva and other body fluids as well as on their red blood cells.

“It didn’t matter how many virus particles we challenged an individual with, if they did not have that first enzyme, they did not get infected,” says researcher Lisa Lindesmith, a virologist at the University of North Carolina in Chapel Hill.
 

No norovirus

Norwalk is a relatively rare type of norovirus. But FUT2 deficiency also provides some protection against the most common strains of norovirus, known as GII.4, which have periodically swept across the world over the past quarter-century. These illnesses take an especially heavy toll on children in the developing world, causing malnutrition and contributing to infant and child deaths.

But progress in translating these insights about genetic resistance into drugs or other things that could reduce the burden of noroviruses has been slow.

“The biggest barrier here is lack of ability to study the virus outside of humans,” Lindesmith says.

Noroviruses are very difficult to grow in the lab, “and there’s no small animal model of gastrointestinal illness caused by the viruses.”

We are clearly making giant strides in improving those skills,” says Lindesmith. “But we are just not quite there yet.”

In the years before COVID-19 emerged, tuberculosis was responsible for the largest number of annual worldwide deaths from an infectious disease. It’s a lung disease caused by the bacterium Mycobacterium tuberculosis, and it has been a pandemic for thousands of years.

Some 85%-95% of people with intact immune systems who are infected with TB control the infection and never get active lung disease. And some people who have intense, continuing exposure to the bacterium, which is spread through droplets and aerosols from people with active lung disease, apparently never become infected at all.
 

Thwarting uberculosis

Understanding the ways of these different forms of resistance could help in the search for vaccines, treatments, and other ways to fight tuberculosis, says Elouise Kroon, MD, a graduate student at Stellenbosch University in Cape Town, South Africa.

“What makes it particularly hard to study is the fact that there is no gold standard to measure infection,” she says. “So, what we do is infer infection from two different types of tests” -- a skin test and a blood test that measure different kinds of immune response to molecules from the bacterium.

Dr. Kroon and other researchers have studied resistance to infection by following people living in the same household as those with active lung disease or people who live and work in crowded conditions in high-risk communities. But not all such studies have used the same definition of so-called resisters, documented exposure in the same way, or followed up to ensure that people continue to test negative over the long term.

The best clue that has emerged from studies so far links resistance to infection to certain variations in immune molecules known as HLA class II antigens, says Marlo Möller, PhD, a professor in the TB Host Genetics Research Group at Stellenbosch University.

“That always seems to pop up everywhere. But the rest is not so obvious,” she says. “A lot of the studies don’t find the same thing. It’s different in different populations,” which may be a result of the long evolutionary history between tuberculosis and humans, as well as the fact that different strains of the bacterium are prevalent in different parts of the world.

COVID-19 is a much newer infectious disease, but teasing out how it contributes to both severe illness and resistance to infection is still a major task.
 

Overcoming COVID

Early in the pandemic, research by the COVID Human Genetic Effort, the international consortium that Dr. Spaan is part of, linked severe COVID-19 pneumonia to the lack of immune molecules known as type I interferons and to antibodies produced by the body that destroy these molecules. Together, these mechanisms explain about one-fifth of severe COVID-19 cases, the researchers reported in 2021.

A few studies by other groups have explored resistance to COVID-19 infection, suggesting that reduced risk of contracting the virus is tied to certain blood group factors. People with Type O blood appear to be at slightly reduced risk of infection, for example.

But the studies done so far are designed to find common genetic variations, which generally have a small effect on resistance. Now, genetic researchers are launching an effort to identify genetic resistance factors with a big effect, even if they are vanishingly rare.

The group is recruiting people who did not become infected with COVID-19 despite heavy exposure, such as those living in households where all the other members got sick or people who were exposed to a superspreader event but did not become ill. As with tuberculosis, being certain that someone has not been infected with the virus can be tricky, but the team is using several blood tests to home in on the people most likely to have escaped infection.

They plan to sequence the genomes of these people to identify things that strongly affect infection risk, then do more laboratory studies to try to tease out the means of resistance.

Their work is inspired by earlier efforts to uncover inborn resistance to infections, Dr. Spaan says. Despite the lack of known examples of such resistance, he is optimistic about the possibilities. Those earlier efforts took place in “a different epoch,” before there were rapid sequencing technologies, Dr. Spaan says.

“Now we have modern technologies to do this more systematically.”

The emergence of viral variants such as the Delta and Omicron COVID strains raises the stakes of the work, he continues.

“The need to unravel these inborn mechanisms of resistance to COVID has become even more important because of these new variants and the anticipation that we will have COVID with us for years.”

A version of this article first appeared on WebMD.com.

It is a great mystery of infectious disease: Why are some people seemingly unaffected by illness that harms others? During the COVID-19 pandemic, we’ve seen this play out time and time again when whole families get sick except for one or two fortunate family members. And at so-called superspreader events that infect many, a lucky few typically walk away with their health intact. Did the virus never enter their bodies? Or do some people have natural resistance to pathogens they’ve never been exposed to before encoded in their genes?

Resistance to infectious disease is much more than a scientific curiosity and studying how it works can be a path to curb future outbreaks.

“In the event that we could identify what makes some people resistant, that immediately opens avenues for therapeutics that we could apply in all those other people who do suffer from the disease,” says András Spaan, MD, a microbiologist at Rockefeller University in New York.

Dr. Spaan is part of an international effort to identify genetic variations that spare people from becoming infected with SARS-CoV-2, the virus that causes COVID-19.

There’s far more research on what drives the tendency to get infectious diseases than on resistance to them. But a few researchers are investigating resistance to some of the world’s most common and deadly infectious diseases, and in a few cases, they’ve already translated these insights into treatments.

Perhaps the strongest example of how odd genes of just a few people can inspire treatments to help many comes from research on the human immunodeficiency virus (HIV), the virus that causes acquired immune deficiency syndrome (AIDS).
 

A genetic quirk

In the mid-1990s, several groups of researchers independently identified a mutation in a gene called CCR5 linked to resistance to HIV infection.

The gene encodes a protein on the surface of some white blood cells that helps set up the movement of other immune cells to fight infections. HIV, meanwhile, uses the CCR5 protein to help it enter the white blood cells that it infects.

The mutation, known as delta 32, results in a shorter than usual protein that doesn’t reach the surface of the cell. People who carry two copies of the delta 32 form of CCR5 do not have any CCR5 protein on the outside of their white blood cells.

Researchers, led by molecular immunologist Philip Murphy, MD, at the National Institute of Allergy and Infectious Diseases in Bethesda, Md, showed in 1997 that people with two copies of the mutation were unusually common among a group of men who were at especially high risk of HIV exposure, but had never contracted the virus. And out of more than 700 HIV-positive people, none carried two copies of CCR5 delta 32.

Pharmaceutical companies used these insights to develop drugs to block CCR5 and delay the development of AIDS. For instance, the drug maraviroc, marketed by Pfizer, was approved for use in HIV-positive people in 2007.

Only a few examples of this kind of inborn, genetically determined complete resistance to infection have ever been heard of. All of them involve cell-surface molecules that are believed to help a virus or other pathogen gain entry to the cell.
 

Locking out illness

“The first step for any intracellular pathogen is getting inside the cell. And if you’re missing the doorway, then the virus can’t accomplish the first step in its life cycle,” Dr. Murphy says. “Getting inside is fundamental.”

Changes in cell-surface molecules can also make someone more likely to have an infection or severe disease. One such group of cell-surface molecules that have been linked to both increasing and decreasing the risk of various infections are histo-blood group antigens. The most familiar members of this group are the molecules that define blood types A, B, and O.

Scientists have also identified one example of total resistance to infection involving these molecules. In 2003, researchers showed that people who lack a functional copy of a gene known as FUT2 cannot be infected with Norwalk virus, one of more than 30 viruses in the norovirus family that cause illness in the digestive tract.

The gene FUT2 encodes an enzyme that determines whether or not blood group antigens are found in a person’s saliva and other body fluids as well as on their red blood cells.

“It didn’t matter how many virus particles we challenged an individual with, if they did not have that first enzyme, they did not get infected,” says researcher Lisa Lindesmith, a virologist at the University of North Carolina in Chapel Hill.
 

No norovirus

Norwalk is a relatively rare type of norovirus. But FUT2 deficiency also provides some protection against the most common strains of norovirus, known as GII.4, which have periodically swept across the world over the past quarter-century. These illnesses take an especially heavy toll on children in the developing world, causing malnutrition and contributing to infant and child deaths.

But progress in translating these insights about genetic resistance into drugs or other things that could reduce the burden of noroviruses has been slow.

“The biggest barrier here is lack of ability to study the virus outside of humans,” Lindesmith says.

Noroviruses are very difficult to grow in the lab, “and there’s no small animal model of gastrointestinal illness caused by the viruses.”

We are clearly making giant strides in improving those skills,” says Lindesmith. “But we are just not quite there yet.”

In the years before COVID-19 emerged, tuberculosis was responsible for the largest number of annual worldwide deaths from an infectious disease. It’s a lung disease caused by the bacterium Mycobacterium tuberculosis, and it has been a pandemic for thousands of years.

Some 85%-95% of people with intact immune systems who are infected with TB control the infection and never get active lung disease. And some people who have intense, continuing exposure to the bacterium, which is spread through droplets and aerosols from people with active lung disease, apparently never become infected at all.
 

Thwarting uberculosis

Understanding the ways of these different forms of resistance could help in the search for vaccines, treatments, and other ways to fight tuberculosis, says Elouise Kroon, MD, a graduate student at Stellenbosch University in Cape Town, South Africa.

“What makes it particularly hard to study is the fact that there is no gold standard to measure infection,” she says. “So, what we do is infer infection from two different types of tests” -- a skin test and a blood test that measure different kinds of immune response to molecules from the bacterium.

Dr. Kroon and other researchers have studied resistance to infection by following people living in the same household as those with active lung disease or people who live and work in crowded conditions in high-risk communities. But not all such studies have used the same definition of so-called resisters, documented exposure in the same way, or followed up to ensure that people continue to test negative over the long term.

The best clue that has emerged from studies so far links resistance to infection to certain variations in immune molecules known as HLA class II antigens, says Marlo Möller, PhD, a professor in the TB Host Genetics Research Group at Stellenbosch University.

“That always seems to pop up everywhere. But the rest is not so obvious,” she says. “A lot of the studies don’t find the same thing. It’s different in different populations,” which may be a result of the long evolutionary history between tuberculosis and humans, as well as the fact that different strains of the bacterium are prevalent in different parts of the world.

COVID-19 is a much newer infectious disease, but teasing out how it contributes to both severe illness and resistance to infection is still a major task.
 

Overcoming COVID

Early in the pandemic, research by the COVID Human Genetic Effort, the international consortium that Dr. Spaan is part of, linked severe COVID-19 pneumonia to the lack of immune molecules known as type I interferons and to antibodies produced by the body that destroy these molecules. Together, these mechanisms explain about one-fifth of severe COVID-19 cases, the researchers reported in 2021.

A few studies by other groups have explored resistance to COVID-19 infection, suggesting that reduced risk of contracting the virus is tied to certain blood group factors. People with Type O blood appear to be at slightly reduced risk of infection, for example.

But the studies done so far are designed to find common genetic variations, which generally have a small effect on resistance. Now, genetic researchers are launching an effort to identify genetic resistance factors with a big effect, even if they are vanishingly rare.

The group is recruiting people who did not become infected with COVID-19 despite heavy exposure, such as those living in households where all the other members got sick or people who were exposed to a superspreader event but did not become ill. As with tuberculosis, being certain that someone has not been infected with the virus can be tricky, but the team is using several blood tests to home in on the people most likely to have escaped infection.

They plan to sequence the genomes of these people to identify things that strongly affect infection risk, then do more laboratory studies to try to tease out the means of resistance.

Their work is inspired by earlier efforts to uncover inborn resistance to infections, Dr. Spaan says. Despite the lack of known examples of such resistance, he is optimistic about the possibilities. Those earlier efforts took place in “a different epoch,” before there were rapid sequencing technologies, Dr. Spaan says.

“Now we have modern technologies to do this more systematically.”

The emergence of viral variants such as the Delta and Omicron COVID strains raises the stakes of the work, he continues.

“The need to unravel these inborn mechanisms of resistance to COVID has become even more important because of these new variants and the anticipation that we will have COVID with us for years.”

A version of this article first appeared on WebMD.com.

Americans who have received a COVID-19 booster shot are 97 times less likely to die from the coronavirus than those who aren’t vaccinated, according to a new update from the CDC.

In addition, fully vaccinated Americans — meaning those with up to two doses, but no booster — are 14 times less likely to die from COVID-19 than unvaccinated people.

“These data confirm that vaccination and boosting continues to protect against severe illness and hospitalization, even during the Omicron surge,” Rochelle Walensky, MD, director of the CDC, said during a briefing by the White House COVID-19 Response Team.

“If you are not up to date on your COVID-19 vaccinations, you have not optimized your protection against severe disease and death, and you should get vaccinated and boosted if you are eligible,” she said.

Dr. Walensky presented the latest numbers on Feb. 2 based on reports from 25 jurisdictions in early December. The number of average weekly deaths for those who were unvaccinated was 9.7 per 100,000 people, as compared with 0.7 of those who were vaccinated and 0.1 of those who had received a booster.

“The data are really stunningly obvious why a booster is really very important,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said during the briefing.

Dr. Fauci also encouraged vaccination for those who are pregnant and couples who may want to conceive in the near feature. He highlighted two recent studies that found vaccination in either partner didn’t affect fertility, including in vitro fertilization.

Meanwhile, fertility fell temporarily among men who were infected with the coronavirus. Couples were 18% less likely to conceive if the male partner had contracted the coronavirus within 60 days before a menstrual cycle.

“New data adds to previous studies that indicate that COVID-19 vaccination does not negatively impact fertility,” Dr. Fauci said. “Vaccination is recommended for people who are trying to get pregnant now or might become pregnant in the future, as well as their partners.”

About 80% of eligible Americans have received at least one vaccine dose, and 68% are fully vaccinated, according to the latest CDC data. About 51% of those who are eligible for a booster dose have received one.

The FDA could authorize the Pfizer vaccine for children under age 5 later this month. When that happens, about 18 million children will qualify for a shot, Jeff Zients, coordinator of the White House COVID-19 Response Team, said during the briefing. The Biden administration is already working on distribution plans for the shot for young kids, he added.

“We’ll be ready to start getting shots in arms soon after FDA and CDC make their decisions,” he said.

A version of this article first appeared on WebMD.com.

Americans who have received a COVID-19 booster shot are 97 times less likely to die from the coronavirus than those who aren’t vaccinated, according to a new update from the CDC.

In addition, fully vaccinated Americans — meaning those with up to two doses, but no booster — are 14 times less likely to die from COVID-19 than unvaccinated people.

“These data confirm that vaccination and boosting continues to protect against severe illness and hospitalization, even during the Omicron surge,” Rochelle Walensky, MD, director of the CDC, said during a briefing by the White House COVID-19 Response Team.

“If you are not up to date on your COVID-19 vaccinations, you have not optimized your protection against severe disease and death, and you should get vaccinated and boosted if you are eligible,” she said.

Dr. Walensky presented the latest numbers on Feb. 2 based on reports from 25 jurisdictions in early December. The number of average weekly deaths for those who were unvaccinated was 9.7 per 100,000 people, as compared with 0.7 of those who were vaccinated and 0.1 of those who had received a booster.

“The data are really stunningly obvious why a booster is really very important,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said during the briefing.

Dr. Fauci also encouraged vaccination for those who are pregnant and couples who may want to conceive in the near feature. He highlighted two recent studies that found vaccination in either partner didn’t affect fertility, including in vitro fertilization.

Meanwhile, fertility fell temporarily among men who were infected with the coronavirus. Couples were 18% less likely to conceive if the male partner had contracted the coronavirus within 60 days before a menstrual cycle.

“New data adds to previous studies that indicate that COVID-19 vaccination does not negatively impact fertility,” Dr. Fauci said. “Vaccination is recommended for people who are trying to get pregnant now or might become pregnant in the future, as well as their partners.”

About 80% of eligible Americans have received at least one vaccine dose, and 68% are fully vaccinated, according to the latest CDC data. About 51% of those who are eligible for a booster dose have received one.

The FDA could authorize the Pfizer vaccine for children under age 5 later this month. When that happens, about 18 million children will qualify for a shot, Jeff Zients, coordinator of the White House COVID-19 Response Team, said during the briefing. The Biden administration is already working on distribution plans for the shot for young kids, he added.

“We’ll be ready to start getting shots in arms soon after FDA and CDC make their decisions,” he said.

A version of this article first appeared on WebMD.com.

Americans who have received a COVID-19 booster shot are 97 times less likely to die from the coronavirus than those who aren’t vaccinated, according to a new update from the CDC.

In addition, fully vaccinated Americans — meaning those with up to two doses, but no booster — are 14 times less likely to die from COVID-19 than unvaccinated people.

“These data confirm that vaccination and boosting continues to protect against severe illness and hospitalization, even during the Omicron surge,” Rochelle Walensky, MD, director of the CDC, said during a briefing by the White House COVID-19 Response Team.

“If you are not up to date on your COVID-19 vaccinations, you have not optimized your protection against severe disease and death, and you should get vaccinated and boosted if you are eligible,” she said.

Dr. Walensky presented the latest numbers on Feb. 2 based on reports from 25 jurisdictions in early December. The number of average weekly deaths for those who were unvaccinated was 9.7 per 100,000 people, as compared with 0.7 of those who were vaccinated and 0.1 of those who had received a booster.

“The data are really stunningly obvious why a booster is really very important,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said during the briefing.

Dr. Fauci also encouraged vaccination for those who are pregnant and couples who may want to conceive in the near feature. He highlighted two recent studies that found vaccination in either partner didn’t affect fertility, including in vitro fertilization.

Meanwhile, fertility fell temporarily among men who were infected with the coronavirus. Couples were 18% less likely to conceive if the male partner had contracted the coronavirus within 60 days before a menstrual cycle.

“New data adds to previous studies that indicate that COVID-19 vaccination does not negatively impact fertility,” Dr. Fauci said. “Vaccination is recommended for people who are trying to get pregnant now or might become pregnant in the future, as well as their partners.”

About 80% of eligible Americans have received at least one vaccine dose, and 68% are fully vaccinated, according to the latest CDC data. About 51% of those who are eligible for a booster dose have received one.

The FDA could authorize the Pfizer vaccine for children under age 5 later this month. When that happens, about 18 million children will qualify for a shot, Jeff Zients, coordinator of the White House COVID-19 Response Team, said during the briefing. The Biden administration is already working on distribution plans for the shot for young kids, he added.

“We’ll be ready to start getting shots in arms soon after FDA and CDC make their decisions,” he said.

A version of this article first appeared on WebMD.com.

A subcutaneous antibody combination of casirivimab and imdevimab given to asymptomatic people who tested positive for SARS-CoV-2 significantly lowered the incidence of symptomatic COVID-19 over 28 days, new research shows.

Results of the study by Meagan P. O’Brien, MD, from Regeneron Pharmaceuticals and one of the study’s funders, and coauthors were published online Jan. 14, 2022, in an original investigation in JAMA.

The results suggest new potential for monoclonal antibodies currently used for postexposure prophylaxis and treatment of symptomatic SARS-CoV-2. It has not been clear whether monoclonal antibodies can benefit people with asymptomatic SARS-CoV-2 infection.

The trial included 314 participants (mean age, 41 years; 51.6% women). Of the participants, 310 (99.7%) completed the efficacy assessment period, and 204 were asymptomatic and tested negative at baseline and were included in the primary efficacy analysis.

The subcutaneous combination of casirivimab and imdevimab, 1,200 mg (600 mg each), significantly prevented progression to symptomatic disease (29/100 [29.0%] vs. 44/104 [42.3%] with placebo; odds ratio, 0.54 [95% confidence interval, 0.30-0.97]; P = .04; absolute risk difference, −13.3% [95% CI, −26.3% to −0.3%]).

These results were part of a randomized, double-blind, placebo-controlled, phase 3 trial of close household contacts of a SARS-CoV-2–infected person at 112 sites in the United States, Romania, and Moldova. They were enrolled between July 13, 2020, and Jan. 28, 2021; follow-up ended March 11, 2021.

Asymptomatic people at least 12 years old were eligible if identified within 96 hours of index case positive test collection and were randomly assigned 1:1 to receive one dose of subcutaneous casirivimab and imdevimab (n = 158), or placebo (n = 156).

COVID-19 vaccination was prohibited before enrollment but was allowed after completing the 28-day efficacy assessment period.
 

Caution warranted

In an accompanying editorial, however, Jonathan Z. Li, MD, Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and Rajesh T. Gandhi, MD, Massachusetts General Hospital, Boston, and Harvard Medical School, urged caution in interpreting the results.

They wrote that, although monoclonal antibodies are generally used in individuals at high risk for severe COVID-19, this study population was less vulnerable, with an average age of 41, and 30% had no risk for the disease.

“Of the remainder, the most common risk factor was being overweight (which confers less risk than other factors),” the editorialists wrote.

They pointed out, as did the study authors, that enrollment came before the emergence of the Delta and Omicron variants, and that both casirivimab and imdevimab maintain their activity against Delta but not against Omicron.

“While prevention of symptomatic infection has benefits,” they wrote, “the primary goal of monoclonal antibody therapy is to prevent progression to severe disease; however, this trial was unable to assess this outcome because there were only three hospitalizations (all in the placebo group). Also, this study was conducted prior to widespread COVID-19 vaccination; whether monoclonal antibodies have the same benefit in people who have breakthrough infection after vaccination is not known.”

The editorialists highlighted the subcutaneous delivery in this study.

They wrote that Dr. O’Brien and coauthors provide evidence that subcutaneous administration is effective in infected individuals. “However, high serum monoclonal antibody levels are achieved more quickly after intravenous administration than following subcutaneous injection; it is unknown whether intravenous administration might have led to even greater efficacy for individuals with asymptomatic SARS-CoV-2 infection.”

The authors of the study also add that, despite efforts to recruit non-White participants, relatively few non-White people were enrolled. Additionally, few adolescents were enrolled.

The sample size was also relatively small, they acknowledge, because of a study design in which the infection status of asymptomatic participants was not confirmed at inclusion.

Several of the authors are employees/stockholders of Regeneron, and have a patent pending, which has been licensed and is receiving royalties. The study was supported by Regeneron and F. Hoffmann–La Roche. This trial was conducted jointly with the National Institute of Allergy and Infectious Diseases and the National Institutes of Health. The CoVPN (COVID-19 Prevention Network) is supported by cooperative agreement awards from the NIAID and NIH.

A version of this article first appeared on Medscape.com.

A subcutaneous antibody combination of casirivimab and imdevimab given to asymptomatic people who tested positive for SARS-CoV-2 significantly lowered the incidence of symptomatic COVID-19 over 28 days, new research shows.

Results of the study by Meagan P. O’Brien, MD, from Regeneron Pharmaceuticals and one of the study’s funders, and coauthors were published online Jan. 14, 2022, in an original investigation in JAMA.

The results suggest new potential for monoclonal antibodies currently used for postexposure prophylaxis and treatment of symptomatic SARS-CoV-2. It has not been clear whether monoclonal antibodies can benefit people with asymptomatic SARS-CoV-2 infection.

The trial included 314 participants (mean age, 41 years; 51.6% women). Of the participants, 310 (99.7%) completed the efficacy assessment period, and 204 were asymptomatic and tested negative at baseline and were included in the primary efficacy analysis.

The subcutaneous combination of casirivimab and imdevimab, 1,200 mg (600 mg each), significantly prevented progression to symptomatic disease (29/100 [29.0%] vs. 44/104 [42.3%] with placebo; odds ratio, 0.54 [95% confidence interval, 0.30-0.97]; P = .04; absolute risk difference, −13.3% [95% CI, −26.3% to −0.3%]).

These results were part of a randomized, double-blind, placebo-controlled, phase 3 trial of close household contacts of a SARS-CoV-2–infected person at 112 sites in the United States, Romania, and Moldova. They were enrolled between July 13, 2020, and Jan. 28, 2021; follow-up ended March 11, 2021.

Asymptomatic people at least 12 years old were eligible if identified within 96 hours of index case positive test collection and were randomly assigned 1:1 to receive one dose of subcutaneous casirivimab and imdevimab (n = 158), or placebo (n = 156).

COVID-19 vaccination was prohibited before enrollment but was allowed after completing the 28-day efficacy assessment period.
 

Caution warranted

In an accompanying editorial, however, Jonathan Z. Li, MD, Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and Rajesh T. Gandhi, MD, Massachusetts General Hospital, Boston, and Harvard Medical School, urged caution in interpreting the results.

They wrote that, although monoclonal antibodies are generally used in individuals at high risk for severe COVID-19, this study population was less vulnerable, with an average age of 41, and 30% had no risk for the disease.

“Of the remainder, the most common risk factor was being overweight (which confers less risk than other factors),” the editorialists wrote.

They pointed out, as did the study authors, that enrollment came before the emergence of the Delta and Omicron variants, and that both casirivimab and imdevimab maintain their activity against Delta but not against Omicron.

“While prevention of symptomatic infection has benefits,” they wrote, “the primary goal of monoclonal antibody therapy is to prevent progression to severe disease; however, this trial was unable to assess this outcome because there were only three hospitalizations (all in the placebo group). Also, this study was conducted prior to widespread COVID-19 vaccination; whether monoclonal antibodies have the same benefit in people who have breakthrough infection after vaccination is not known.”

The editorialists highlighted the subcutaneous delivery in this study.

They wrote that Dr. O’Brien and coauthors provide evidence that subcutaneous administration is effective in infected individuals. “However, high serum monoclonal antibody levels are achieved more quickly after intravenous administration than following subcutaneous injection; it is unknown whether intravenous administration might have led to even greater efficacy for individuals with asymptomatic SARS-CoV-2 infection.”

The authors of the study also add that, despite efforts to recruit non-White participants, relatively few non-White people were enrolled. Additionally, few adolescents were enrolled.

The sample size was also relatively small, they acknowledge, because of a study design in which the infection status of asymptomatic participants was not confirmed at inclusion.

Several of the authors are employees/stockholders of Regeneron, and have a patent pending, which has been licensed and is receiving royalties. The study was supported by Regeneron and F. Hoffmann–La Roche. This trial was conducted jointly with the National Institute of Allergy and Infectious Diseases and the National Institutes of Health. The CoVPN (COVID-19 Prevention Network) is supported by cooperative agreement awards from the NIAID and NIH.

A version of this article first appeared on Medscape.com.

A subcutaneous antibody combination of casirivimab and imdevimab given to asymptomatic people who tested positive for SARS-CoV-2 significantly lowered the incidence of symptomatic COVID-19 over 28 days, new research shows.

Results of the study by Meagan P. O’Brien, MD, from Regeneron Pharmaceuticals and one of the study’s funders, and coauthors were published online Jan. 14, 2022, in an original investigation in JAMA.

The results suggest new potential for monoclonal antibodies currently used for postexposure prophylaxis and treatment of symptomatic SARS-CoV-2. It has not been clear whether monoclonal antibodies can benefit people with asymptomatic SARS-CoV-2 infection.

The trial included 314 participants (mean age, 41 years; 51.6% women). Of the participants, 310 (99.7%) completed the efficacy assessment period, and 204 were asymptomatic and tested negative at baseline and were included in the primary efficacy analysis.

The subcutaneous combination of casirivimab and imdevimab, 1,200 mg (600 mg each), significantly prevented progression to symptomatic disease (29/100 [29.0%] vs. 44/104 [42.3%] with placebo; odds ratio, 0.54 [95% confidence interval, 0.30-0.97]; P = .04; absolute risk difference, −13.3% [95% CI, −26.3% to −0.3%]).

These results were part of a randomized, double-blind, placebo-controlled, phase 3 trial of close household contacts of a SARS-CoV-2–infected person at 112 sites in the United States, Romania, and Moldova. They were enrolled between July 13, 2020, and Jan. 28, 2021; follow-up ended March 11, 2021.

Asymptomatic people at least 12 years old were eligible if identified within 96 hours of index case positive test collection and were randomly assigned 1:1 to receive one dose of subcutaneous casirivimab and imdevimab (n = 158), or placebo (n = 156).

COVID-19 vaccination was prohibited before enrollment but was allowed after completing the 28-day efficacy assessment period.
 

Caution warranted

In an accompanying editorial, however, Jonathan Z. Li, MD, Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and Rajesh T. Gandhi, MD, Massachusetts General Hospital, Boston, and Harvard Medical School, urged caution in interpreting the results.

They wrote that, although monoclonal antibodies are generally used in individuals at high risk for severe COVID-19, this study population was less vulnerable, with an average age of 41, and 30% had no risk for the disease.

“Of the remainder, the most common risk factor was being overweight (which confers less risk than other factors),” the editorialists wrote.

They pointed out, as did the study authors, that enrollment came before the emergence of the Delta and Omicron variants, and that both casirivimab and imdevimab maintain their activity against Delta but not against Omicron.

“While prevention of symptomatic infection has benefits,” they wrote, “the primary goal of monoclonal antibody therapy is to prevent progression to severe disease; however, this trial was unable to assess this outcome because there were only three hospitalizations (all in the placebo group). Also, this study was conducted prior to widespread COVID-19 vaccination; whether monoclonal antibodies have the same benefit in people who have breakthrough infection after vaccination is not known.”

The editorialists highlighted the subcutaneous delivery in this study.

They wrote that Dr. O’Brien and coauthors provide evidence that subcutaneous administration is effective in infected individuals. “However, high serum monoclonal antibody levels are achieved more quickly after intravenous administration than following subcutaneous injection; it is unknown whether intravenous administration might have led to even greater efficacy for individuals with asymptomatic SARS-CoV-2 infection.”

The authors of the study also add that, despite efforts to recruit non-White participants, relatively few non-White people were enrolled. Additionally, few adolescents were enrolled.

The sample size was also relatively small, they acknowledge, because of a study design in which the infection status of asymptomatic participants was not confirmed at inclusion.

Several of the authors are employees/stockholders of Regeneron, and have a patent pending, which has been licensed and is receiving royalties. The study was supported by Regeneron and F. Hoffmann–La Roche. This trial was conducted jointly with the National Institute of Allergy and Infectious Diseases and the National Institutes of Health. The CoVPN (COVID-19 Prevention Network) is supported by cooperative agreement awards from the NIAID and NIH.

A version of this article first appeared on Medscape.com.

Many factors influence a child’s subsequent susceptibility to respiratory tract infection (RTI), including breastfeeding, crowded conditions, and exposure to environmental tobacco. Now researchers have found that asymptomatic viral infection in the first days of a baby’s life are linked to a greater risk of respiratory infections in later life.

The new research, published in Nature Microbiology, was conducted as part of the Microbiome Utrecht Infant Study (MUIS), a healthy infant birth cohort study that’s been running for 6 years.

In their study, the authors explained how the respiratory tract is “populated by a specialized microbial ecosystem, which is seeded during and directly following birth,” adding that, “despite recognition of many host and environmental factors known to modulate RTI susceptibility, the mechanism by which a child develops recurrent or severe RTIs, while others remain healthy, remains largely unknown”.

Researchers from the University of Edinburgh and University Medical Centre Utrecht (the Netherlands) examined nasal mucosa samples of 114 babies at various times from birth until 12 months of age. They then analyzed the gene activity of the babies’ nasal mucosa, the microbes present in the lining of the nose, and any viruses that infected the children.
 

Interferon-related mucosal gene activity

The researchers described how the microbiome – the community of microbes in the body – of a newborn baby can be influenced by many things, including delivery method, breastfeeding, antibiotics and the hospital environment. They highlighted how viruses were found to interact with a newborn’s immune system and microbiome in a way that affected both a child’s risk, and number, of subsequent infections.

They explained how when a viral infection was detected in the first days after birth, which they said largely occurred asymptomatically, specific mucosal genes were activated – genes involved with interferons – coinciding with a change in the composition of the microbiome, promoting the growth of potentially harmful microbes.

“The interferon-related gene activity caused by an early first viral infection is thought to create a proinflammatory environment that makes babies susceptible to future infections,” they said, adding that in their study they have demonstrated that “first asymptomatic viral encounters were associated with increased interferon signaling, and preceded the development of disadvantageous respiratory microbiota profiles and clinical RTIs”.
 

Proinflammatory and microbiologically perturbed environment

Debby Bogaert, PhD, chair of paediatric medicine at the University of Edinburgh, said: “We were surprised to see viral infections occur so early in life, and go mostly unnoticed, probably because the infant’s immune system is in what is known as a state of tolerance after birth. Despite this, these infections seem to affect a normal immune development, which is important to know.”

The authors wrote that their data supports the hypothesis that first viral encounters trigger an interferon-associated proinflammatory environment, which then further drives airway inflammation and symptomatology in a “self-enforcing positive feedback loop”. They said that this “proinflammatory and microbiologically perturbed environment in turn renders an individual more vulnerable to recurrent viral-induced RTIs”.

Wouter de Steenhuijsen, PhD, postdoctoral investigator at University Medical Centre Utrecht, said: “Although further work will be needed to confirm the causality of our findings, the data from this study indicate that early-life encounters with respiratory viruses – especially during the first days of life – may set the tone for subsequent non-beneficial host-microbe interactions, which are related to an infection risk and possibly long term respiratory health.”

Dr. Bogaert added: “Only from birth onwards will an infant start to develop its microbiome. Limiting the number of viral encounters in those first days to weeks of life might be essential for a healthy immune and microbiome development, and consequently long term respiratory health.”

A version of this article first appeared on Medscape UK.

Many factors influence a child’s subsequent susceptibility to respiratory tract infection (RTI), including breastfeeding, crowded conditions, and exposure to environmental tobacco. Now researchers have found that asymptomatic viral infection in the first days of a baby’s life are linked to a greater risk of respiratory infections in later life.

The new research, published in Nature Microbiology, was conducted as part of the Microbiome Utrecht Infant Study (MUIS), a healthy infant birth cohort study that’s been running for 6 years.

In their study, the authors explained how the respiratory tract is “populated by a specialized microbial ecosystem, which is seeded during and directly following birth,” adding that, “despite recognition of many host and environmental factors known to modulate RTI susceptibility, the mechanism by which a child develops recurrent or severe RTIs, while others remain healthy, remains largely unknown”.

Researchers from the University of Edinburgh and University Medical Centre Utrecht (the Netherlands) examined nasal mucosa samples of 114 babies at various times from birth until 12 months of age. They then analyzed the gene activity of the babies’ nasal mucosa, the microbes present in the lining of the nose, and any viruses that infected the children.
 

Interferon-related mucosal gene activity

The researchers described how the microbiome – the community of microbes in the body – of a newborn baby can be influenced by many things, including delivery method, breastfeeding, antibiotics and the hospital environment. They highlighted how viruses were found to interact with a newborn’s immune system and microbiome in a way that affected both a child’s risk, and number, of subsequent infections.

They explained how when a viral infection was detected in the first days after birth, which they said largely occurred asymptomatically, specific mucosal genes were activated – genes involved with interferons – coinciding with a change in the composition of the microbiome, promoting the growth of potentially harmful microbes.

“The interferon-related gene activity caused by an early first viral infection is thought to create a proinflammatory environment that makes babies susceptible to future infections,” they said, adding that in their study they have demonstrated that “first asymptomatic viral encounters were associated with increased interferon signaling, and preceded the development of disadvantageous respiratory microbiota profiles and clinical RTIs”.
 

Proinflammatory and microbiologically perturbed environment

Debby Bogaert, PhD, chair of paediatric medicine at the University of Edinburgh, said: “We were surprised to see viral infections occur so early in life, and go mostly unnoticed, probably because the infant’s immune system is in what is known as a state of tolerance after birth. Despite this, these infections seem to affect a normal immune development, which is important to know.”

The authors wrote that their data supports the hypothesis that first viral encounters trigger an interferon-associated proinflammatory environment, which then further drives airway inflammation and symptomatology in a “self-enforcing positive feedback loop”. They said that this “proinflammatory and microbiologically perturbed environment in turn renders an individual more vulnerable to recurrent viral-induced RTIs”.

Wouter de Steenhuijsen, PhD, postdoctoral investigator at University Medical Centre Utrecht, said: “Although further work will be needed to confirm the causality of our findings, the data from this study indicate that early-life encounters with respiratory viruses – especially during the first days of life – may set the tone for subsequent non-beneficial host-microbe interactions, which are related to an infection risk and possibly long term respiratory health.”

Dr. Bogaert added: “Only from birth onwards will an infant start to develop its microbiome. Limiting the number of viral encounters in those first days to weeks of life might be essential for a healthy immune and microbiome development, and consequently long term respiratory health.”

A version of this article first appeared on Medscape UK.

Many factors influence a child’s subsequent susceptibility to respiratory tract infection (RTI), including breastfeeding, crowded conditions, and exposure to environmental tobacco. Now researchers have found that asymptomatic viral infection in the first days of a baby’s life are linked to a greater risk of respiratory infections in later life.

The new research, published in Nature Microbiology, was conducted as part of the Microbiome Utrecht Infant Study (MUIS), a healthy infant birth cohort study that’s been running for 6 years.

In their study, the authors explained how the respiratory tract is “populated by a specialized microbial ecosystem, which is seeded during and directly following birth,” adding that, “despite recognition of many host and environmental factors known to modulate RTI susceptibility, the mechanism by which a child develops recurrent or severe RTIs, while others remain healthy, remains largely unknown”.

Researchers from the University of Edinburgh and University Medical Centre Utrecht (the Netherlands) examined nasal mucosa samples of 114 babies at various times from birth until 12 months of age. They then analyzed the gene activity of the babies’ nasal mucosa, the microbes present in the lining of the nose, and any viruses that infected the children.
 

Interferon-related mucosal gene activity

The researchers described how the microbiome – the community of microbes in the body – of a newborn baby can be influenced by many things, including delivery method, breastfeeding, antibiotics and the hospital environment. They highlighted how viruses were found to interact with a newborn’s immune system and microbiome in a way that affected both a child’s risk, and number, of subsequent infections.

They explained how when a viral infection was detected in the first days after birth, which they said largely occurred asymptomatically, specific mucosal genes were activated – genes involved with interferons – coinciding with a change in the composition of the microbiome, promoting the growth of potentially harmful microbes.

“The interferon-related gene activity caused by an early first viral infection is thought to create a proinflammatory environment that makes babies susceptible to future infections,” they said, adding that in their study they have demonstrated that “first asymptomatic viral encounters were associated with increased interferon signaling, and preceded the development of disadvantageous respiratory microbiota profiles and clinical RTIs”.
 

Proinflammatory and microbiologically perturbed environment

Debby Bogaert, PhD, chair of paediatric medicine at the University of Edinburgh, said: “We were surprised to see viral infections occur so early in life, and go mostly unnoticed, probably because the infant’s immune system is in what is known as a state of tolerance after birth. Despite this, these infections seem to affect a normal immune development, which is important to know.”

The authors wrote that their data supports the hypothesis that first viral encounters trigger an interferon-associated proinflammatory environment, which then further drives airway inflammation and symptomatology in a “self-enforcing positive feedback loop”. They said that this “proinflammatory and microbiologically perturbed environment in turn renders an individual more vulnerable to recurrent viral-induced RTIs”.

Wouter de Steenhuijsen, PhD, postdoctoral investigator at University Medical Centre Utrecht, said: “Although further work will be needed to confirm the causality of our findings, the data from this study indicate that early-life encounters with respiratory viruses – especially during the first days of life – may set the tone for subsequent non-beneficial host-microbe interactions, which are related to an infection risk and possibly long term respiratory health.”

Dr. Bogaert added: “Only from birth onwards will an infant start to develop its microbiome. Limiting the number of viral encounters in those first days to weeks of life might be essential for a healthy immune and microbiome development, and consequently long term respiratory health.”

A version of this article first appeared on Medscape UK.

The world’s most valuable mouse

You’ve heard of Mighty Mouse. Now say hello to the world’s newest mouse superhero, Crypto-Mouse! After being bitten by a radioactive cryptocurrency investor, Crypto-Mouse can tap directly into the power of the blockchain itself, allowing it to perform incredible, death-defying feats of strength!

We’re going to stop right there before Crypto-Mouse gains entry into the Marvel cinematic universe. Let’s rewind to the beginning, because that’s precisely where this crazy scheme is at. In late January, a new decentralized autonomous organization, BitMouseDAO, launched to enormous … -ly little fanfare, according to Vice. Two investors as of Jan. 31. But what they lack in money they make up for in sheer ambition.

Clker-Free-Vector-Images/Pixabay

BitMouseDAO’s $100 million dollar idea is to genetically engineer mice to carry bitcoin, the first cryptocurrency and one of the most valuable. This isn’t as crazy an idea as it sounds since DNA can be modified to store information, potentially even bitcoin information. Their plan is to create a private bitcoin wallet, which will be stored in the mouse DNA, and purchase online bitcoin to store in this wallet.

BitMouseDAO, being a “collection of artists,” plans to partner with a lab to translate its private key into a specific DNA sequence to be encoded into the mice during fertilization; or, if that doesn’t work, inject them with a harmless virus that carries the key.

Since these are artists, their ultimate plan is to use their bitcoin mice to make NFTs (scratch that off your cryptocurrency bingo card) and auction them off to people. Or, as Vice put it, BitMouseDAO essentially plans to send preserved dead mice to people. Artistic dead mice! Artistic dead mice worth millions! Maybe. Even BitMouseDAO admits bitcoin could be worthless by the time the project gets off the ground.

If this all sounds completely insane, that’s because it is. But it also sounds crazy enough to work. Now, if you’ll excuse us, we’re off to write a screenplay about a scrappy group of high-tech thieves who steal a group of genetically altered bitcoin mice to sell for millions, only to keep them as their adorable pets. Trust us Hollywood, it’ll make millions!
 

Alcoholic monkeys vs. the future of feces

Which is more important, the journey or the destination? Science is all about the destination, yes? Solving the problem, saving a life, expanding horizons. That’s science. Or is it? The scientific method is a process, so does that make it a journey?

Amandad/Pixabay

For us, today’s journey begins at the University of Iowa, where investigators are trying to reduce alcohol consumption. A worthy goal, and they seem to have made some progress by targeting a liver hormone called fibroblast growth factor 21 (FGF21). But we’re more interested in the process right now, so bring on the alcoholic monkeys. And no, that’s not a death metal/reggae fusion band. Should be, though.

“The vervet monkey population is [composed] of alcohol avoiders, moderate alcohol drinkers, and a group of heavy drinkers,” Matthew Potthoff, PhD, and associates wrote in Cell Metabolism. When this particular bunch of heavy-drinking vervets were given FGF21, they consumed 50% less alcohol than did vehicle-treated controls, so mission accomplished.

Maybe it could be a breakfast cereal. Who wouldn’t enjoy a bowl of alcoholic monkeys in the morning?

And after breakfast, you might be ready for a digitized bowel movement, courtesy of researchers at University of California, San Diego. They’re studying ulcerative colitis (UC) by examining the gut microbiome, and their “most useful biological sample is patient stool,” according to a written statement from the university.

“Once we had all the technology to digitize the stool, the question was, is this going to tell us what’s happening in these patients? The answer turned out to be yes,” co-senior author Rob Knight, PhD, said in the statement. “Digitizing fecal material is the future.” The road to UC treatment, in other words, is paved with digital stool.

About 40% of the UC patients had elevated protease levels, and their high-protease feces were then transplanted into germ-free mice, which subsequently developed colitis and were successfully treated with protease inhibitors. And that is our final destination.

As our revered founder and mentor, Josephine Lotmevich, used to say, an alcoholic monkey in the hand is worth a number 2 in the bush.
 

Raise a glass to delinquency

You wouldn’t think that a glass of water could lead to a life of crime, but a recent study suggests just that.

PxHere

Children exposed to lead in their drinking water during their early years had a 21% higher risk of delinquency after the age of 14 years and a 38% higher risk of having a record for a serious complaint, Jackie MacDonald Gibson and associates said in a statement on Eurekalert.

Data for the study came from Wake County, N.C., which includes rural areas, wealthy exurban developments, and predominantly Black communities. The investigators compared the blood lead levels for children tested between 1998 and 2011 with juvenile delinquency reports of the same children from the N.C. Department of Public Safety.

The main culprit, they found, was well water. Blood lead levels were 11% higher in the children whose water came from private wells, compared with children using community water. About 13% of U.S. households rely on private wells, which are not regulated under the Safe Drinking Water Act, for their water supply.

The researchers said there is an urgent need for better drinking-water solutions in communities that rely on well water, whether it be through subsidized home filtration or infrastructure redevelopment.

An earlier study had estimated that preventing just one child from entering the adult criminal justice system would save $1.3 to $1.5 million in 1997 dollars. That’s about $2.2 to $2.5 million dollars today!

If you do the math, it’s not hard to see what’s cheaper (and healthier) in the long run.
 

A ‘dirty’ scam

Another one? This is just getting sad. You’ve probably heard of muds and clays being good for the skin and maybe you’ve gone to a spa and sat in a mud bath, but would you believe it if someone told you that mud can cure all your ailments? No? Neither would we. Senatorial candidate Beto O’Rourke was definitely someone who brought this strange treatment to light, but it seems like this is something that has been going on for years, even before the pandemic.

Nandan/Pixahive

A company called Black Oxygen Organics (BOO) was selling “magic dirt” for $110 per 4-ounce package. It claimed the dirt was high in fulvic acid and humic acid, which are good for many things. They were, however, literally getting this mud from bogs with landfills nearby, Mel magazine reported.

That doesn’t sound appealing at all, but wait, there’s more. People were eating, drinking, bathing, and feeding their families this sludge in hopes that they would be cured of their ailments. A lot of people jumped aboard the magic dirt train when the pandemic arose, but it quickly became clear that this mud was not as helpful as BOO claimed it to be.

“We began to receive inquiries and calls on our website with people having problems and issues. Ultimately, we sent the products out for independent testing, and then when that came back and showed that there were toxic heavy metals [lead, arsenic, and cadmium among them] at an unsafe level, that’s when we knew we had to act,” Atlanta-based attorney Matt Wetherington, who filed a federal lawsuit against BOO, told Mel.

After a very complicated series of events involving an expose by NBC, product recalls, extortion claims, and grassroots activism, BOO was shut down by both the Canadian and U.S. governments.

As always, please listen only to health care professionals when you wish to use natural remedies for illnesses and ailments.

The world’s most valuable mouse

You’ve heard of Mighty Mouse. Now say hello to the world’s newest mouse superhero, Crypto-Mouse! After being bitten by a radioactive cryptocurrency investor, Crypto-Mouse can tap directly into the power of the blockchain itself, allowing it to perform incredible, death-defying feats of strength!

We’re going to stop right there before Crypto-Mouse gains entry into the Marvel cinematic universe. Let’s rewind to the beginning, because that’s precisely where this crazy scheme is at. In late January, a new decentralized autonomous organization, BitMouseDAO, launched to enormous … -ly little fanfare, according to Vice. Two investors as of Jan. 31. But what they lack in money they make up for in sheer ambition.

Clker-Free-Vector-Images/Pixabay

BitMouseDAO’s $100 million dollar idea is to genetically engineer mice to carry bitcoin, the first cryptocurrency and one of the most valuable. This isn’t as crazy an idea as it sounds since DNA can be modified to store information, potentially even bitcoin information. Their plan is to create a private bitcoin wallet, which will be stored in the mouse DNA, and purchase online bitcoin to store in this wallet.

BitMouseDAO, being a “collection of artists,” plans to partner with a lab to translate its private key into a specific DNA sequence to be encoded into the mice during fertilization; or, if that doesn’t work, inject them with a harmless virus that carries the key.

Since these are artists, their ultimate plan is to use their bitcoin mice to make NFTs (scratch that off your cryptocurrency bingo card) and auction them off to people. Or, as Vice put it, BitMouseDAO essentially plans to send preserved dead mice to people. Artistic dead mice! Artistic dead mice worth millions! Maybe. Even BitMouseDAO admits bitcoin could be worthless by the time the project gets off the ground.

If this all sounds completely insane, that’s because it is. But it also sounds crazy enough to work. Now, if you’ll excuse us, we’re off to write a screenplay about a scrappy group of high-tech thieves who steal a group of genetically altered bitcoin mice to sell for millions, only to keep them as their adorable pets. Trust us Hollywood, it’ll make millions!
 

Alcoholic monkeys vs. the future of feces

Which is more important, the journey or the destination? Science is all about the destination, yes? Solving the problem, saving a life, expanding horizons. That’s science. Or is it? The scientific method is a process, so does that make it a journey?

Amandad/Pixabay

For us, today’s journey begins at the University of Iowa, where investigators are trying to reduce alcohol consumption. A worthy goal, and they seem to have made some progress by targeting a liver hormone called fibroblast growth factor 21 (FGF21). But we’re more interested in the process right now, so bring on the alcoholic monkeys. And no, that’s not a death metal/reggae fusion band. Should be, though.

“The vervet monkey population is [composed] of alcohol avoiders, moderate alcohol drinkers, and a group of heavy drinkers,” Matthew Potthoff, PhD, and associates wrote in Cell Metabolism. When this particular bunch of heavy-drinking vervets were given FGF21, they consumed 50% less alcohol than did vehicle-treated controls, so mission accomplished.

Maybe it could be a breakfast cereal. Who wouldn’t enjoy a bowl of alcoholic monkeys in the morning?

And after breakfast, you might be ready for a digitized bowel movement, courtesy of researchers at University of California, San Diego. They’re studying ulcerative colitis (UC) by examining the gut microbiome, and their “most useful biological sample is patient stool,” according to a written statement from the university.

“Once we had all the technology to digitize the stool, the question was, is this going to tell us what’s happening in these patients? The answer turned out to be yes,” co-senior author Rob Knight, PhD, said in the statement. “Digitizing fecal material is the future.” The road to UC treatment, in other words, is paved with digital stool.

About 40% of the UC patients had elevated protease levels, and their high-protease feces were then transplanted into germ-free mice, which subsequently developed colitis and were successfully treated with protease inhibitors. And that is our final destination.

As our revered founder and mentor, Josephine Lotmevich, used to say, an alcoholic monkey in the hand is worth a number 2 in the bush.
 

Raise a glass to delinquency

You wouldn’t think that a glass of water could lead to a life of crime, but a recent study suggests just that.

PxHere

Children exposed to lead in their drinking water during their early years had a 21% higher risk of delinquency after the age of 14 years and a 38% higher risk of having a record for a serious complaint, Jackie MacDonald Gibson and associates said in a statement on Eurekalert.

Data for the study came from Wake County, N.C., which includes rural areas, wealthy exurban developments, and predominantly Black communities. The investigators compared the blood lead levels for children tested between 1998 and 2011 with juvenile delinquency reports of the same children from the N.C. Department of Public Safety.

The main culprit, they found, was well water. Blood lead levels were 11% higher in the children whose water came from private wells, compared with children using community water. About 13% of U.S. households rely on private wells, which are not regulated under the Safe Drinking Water Act, for their water supply.

The researchers said there is an urgent need for better drinking-water solutions in communities that rely on well water, whether it be through subsidized home filtration or infrastructure redevelopment.

An earlier study had estimated that preventing just one child from entering the adult criminal justice system would save $1.3 to $1.5 million in 1997 dollars. That’s about $2.2 to $2.5 million dollars today!

If you do the math, it’s not hard to see what’s cheaper (and healthier) in the long run.
 

A ‘dirty’ scam

Another one? This is just getting sad. You’ve probably heard of muds and clays being good for the skin and maybe you’ve gone to a spa and sat in a mud bath, but would you believe it if someone told you that mud can cure all your ailments? No? Neither would we. Senatorial candidate Beto O’Rourke was definitely someone who brought this strange treatment to light, but it seems like this is something that has been going on for years, even before the pandemic.

Nandan/Pixahive

A company called Black Oxygen Organics (BOO) was selling “magic dirt” for $110 per 4-ounce package. It claimed the dirt was high in fulvic acid and humic acid, which are good for many things. They were, however, literally getting this mud from bogs with landfills nearby, Mel magazine reported.

That doesn’t sound appealing at all, but wait, there’s more. People were eating, drinking, bathing, and feeding their families this sludge in hopes that they would be cured of their ailments. A lot of people jumped aboard the magic dirt train when the pandemic arose, but it quickly became clear that this mud was not as helpful as BOO claimed it to be.

“We began to receive inquiries and calls on our website with people having problems and issues. Ultimately, we sent the products out for independent testing, and then when that came back and showed that there were toxic heavy metals [lead, arsenic, and cadmium among them] at an unsafe level, that’s when we knew we had to act,” Atlanta-based attorney Matt Wetherington, who filed a federal lawsuit against BOO, told Mel.

After a very complicated series of events involving an expose by NBC, product recalls, extortion claims, and grassroots activism, BOO was shut down by both the Canadian and U.S. governments.

As always, please listen only to health care professionals when you wish to use natural remedies for illnesses and ailments.

The world’s most valuable mouse

You’ve heard of Mighty Mouse. Now say hello to the world’s newest mouse superhero, Crypto-Mouse! After being bitten by a radioactive cryptocurrency investor, Crypto-Mouse can tap directly into the power of the blockchain itself, allowing it to perform incredible, death-defying feats of strength!

We’re going to stop right there before Crypto-Mouse gains entry into the Marvel cinematic universe. Let’s rewind to the beginning, because that’s precisely where this crazy scheme is at. In late January, a new decentralized autonomous organization, BitMouseDAO, launched to enormous … -ly little fanfare, according to Vice. Two investors as of Jan. 31. But what they lack in money they make up for in sheer ambition.

Clker-Free-Vector-Images/Pixabay

BitMouseDAO’s $100 million dollar idea is to genetically engineer mice to carry bitcoin, the first cryptocurrency and one of the most valuable. This isn’t as crazy an idea as it sounds since DNA can be modified to store information, potentially even bitcoin information. Their plan is to create a private bitcoin wallet, which will be stored in the mouse DNA, and purchase online bitcoin to store in this wallet.

BitMouseDAO, being a “collection of artists,” plans to partner with a lab to translate its private key into a specific DNA sequence to be encoded into the mice during fertilization; or, if that doesn’t work, inject them with a harmless virus that carries the key.

Since these are artists, their ultimate plan is to use their bitcoin mice to make NFTs (scratch that off your cryptocurrency bingo card) and auction them off to people. Or, as Vice put it, BitMouseDAO essentially plans to send preserved dead mice to people. Artistic dead mice! Artistic dead mice worth millions! Maybe. Even BitMouseDAO admits bitcoin could be worthless by the time the project gets off the ground.

If this all sounds completely insane, that’s because it is. But it also sounds crazy enough to work. Now, if you’ll excuse us, we’re off to write a screenplay about a scrappy group of high-tech thieves who steal a group of genetically altered bitcoin mice to sell for millions, only to keep them as their adorable pets. Trust us Hollywood, it’ll make millions!
 

Alcoholic monkeys vs. the future of feces

Which is more important, the journey or the destination? Science is all about the destination, yes? Solving the problem, saving a life, expanding horizons. That’s science. Or is it? The scientific method is a process, so does that make it a journey?

Amandad/Pixabay

For us, today’s journey begins at the University of Iowa, where investigators are trying to reduce alcohol consumption. A worthy goal, and they seem to have made some progress by targeting a liver hormone called fibroblast growth factor 21 (FGF21). But we’re more interested in the process right now, so bring on the alcoholic monkeys. And no, that’s not a death metal/reggae fusion band. Should be, though.

“The vervet monkey population is [composed] of alcohol avoiders, moderate alcohol drinkers, and a group of heavy drinkers,” Matthew Potthoff, PhD, and associates wrote in Cell Metabolism. When this particular bunch of heavy-drinking vervets were given FGF21, they consumed 50% less alcohol than did vehicle-treated controls, so mission accomplished.

Maybe it could be a breakfast cereal. Who wouldn’t enjoy a bowl of alcoholic monkeys in the morning?

And after breakfast, you might be ready for a digitized bowel movement, courtesy of researchers at University of California, San Diego. They’re studying ulcerative colitis (UC) by examining the gut microbiome, and their “most useful biological sample is patient stool,” according to a written statement from the university.

“Once we had all the technology to digitize the stool, the question was, is this going to tell us what’s happening in these patients? The answer turned out to be yes,” co-senior author Rob Knight, PhD, said in the statement. “Digitizing fecal material is the future.” The road to UC treatment, in other words, is paved with digital stool.

About 40% of the UC patients had elevated protease levels, and their high-protease feces were then transplanted into germ-free mice, which subsequently developed colitis and were successfully treated with protease inhibitors. And that is our final destination.

As our revered founder and mentor, Josephine Lotmevich, used to say, an alcoholic monkey in the hand is worth a number 2 in the bush.
 

Raise a glass to delinquency

You wouldn’t think that a glass of water could lead to a life of crime, but a recent study suggests just that.

PxHere

Children exposed to lead in their drinking water during their early years had a 21% higher risk of delinquency after the age of 14 years and a 38% higher risk of having a record for a serious complaint, Jackie MacDonald Gibson and associates said in a statement on Eurekalert.

Data for the study came from Wake County, N.C., which includes rural areas, wealthy exurban developments, and predominantly Black communities. The investigators compared the blood lead levels for children tested between 1998 and 2011 with juvenile delinquency reports of the same children from the N.C. Department of Public Safety.

The main culprit, they found, was well water. Blood lead levels were 11% higher in the children whose water came from private wells, compared with children using community water. About 13% of U.S. households rely on private wells, which are not regulated under the Safe Drinking Water Act, for their water supply.

The researchers said there is an urgent need for better drinking-water solutions in communities that rely on well water, whether it be through subsidized home filtration or infrastructure redevelopment.

An earlier study had estimated that preventing just one child from entering the adult criminal justice system would save $1.3 to $1.5 million in 1997 dollars. That’s about $2.2 to $2.5 million dollars today!

If you do the math, it’s not hard to see what’s cheaper (and healthier) in the long run.
 

A ‘dirty’ scam

Another one? This is just getting sad. You’ve probably heard of muds and clays being good for the skin and maybe you’ve gone to a spa and sat in a mud bath, but would you believe it if someone told you that mud can cure all your ailments? No? Neither would we. Senatorial candidate Beto O’Rourke was definitely someone who brought this strange treatment to light, but it seems like this is something that has been going on for years, even before the pandemic.

Nandan/Pixahive

A company called Black Oxygen Organics (BOO) was selling “magic dirt” for $110 per 4-ounce package. It claimed the dirt was high in fulvic acid and humic acid, which are good for many things. They were, however, literally getting this mud from bogs with landfills nearby, Mel magazine reported.

That doesn’t sound appealing at all, but wait, there’s more. People were eating, drinking, bathing, and feeding their families this sludge in hopes that they would be cured of their ailments. A lot of people jumped aboard the magic dirt train when the pandemic arose, but it quickly became clear that this mud was not as helpful as BOO claimed it to be.

“We began to receive inquiries and calls on our website with people having problems and issues. Ultimately, we sent the products out for independent testing, and then when that came back and showed that there were toxic heavy metals [lead, arsenic, and cadmium among them] at an unsafe level, that’s when we knew we had to act,” Atlanta-based attorney Matt Wetherington, who filed a federal lawsuit against BOO, told Mel.

After a very complicated series of events involving an expose by NBC, product recalls, extortion claims, and grassroots activism, BOO was shut down by both the Canadian and U.S. governments.

As always, please listen only to health care professionals when you wish to use natural remedies for illnesses and ailments.

Hospitalized intensive care patients with respiratory syncytial virus were significantly more likely to be immunocompromised and to have chronic respiratory conditions than those with influenza infections, but in-hospital mortality rates were similar, based on data from 618 adults.

Respiratory syncytial virus is common in adults, but characteristics of RSV patients requiring ICU care have not been explored, despite routine testing for RSV in critically ill patients in many institutions, Julien Coussement, PhD, of Université Libre de Bruxelles, Brussels, and colleagues wrote.

“Influenza is another respiratory virus routinely tested for in ICU patients with respiratory symptoms because of its well-known morbidity and mortality, but there are no data specifically comparing RSV and influenza infections in adult ICU patients,” they noted.

In a retrospective, multicenter study published in the journal CHEST, the researchers analyzed data from 309 adult ICU patients with RSV infection and 309 with influenza infection between November 2011 and April 2018 from 17 sites in France and Belgium. Each RSV patient was matched to a flu patient according to institution and date of diagnosis.

The primary objective was a comparison of in-hospital mortality between the groups, defined as death from any cause during an index hospital stay in acute care. Secondary objectives were comparisons of the clinical and biological characteristics of patients with RSV versus flu.

Overall, in-hospital mortality was not significantly different between the RSV and influenza groups (23.9% vs. 25.6%, P = .63).

However, patients with RSV infection were significantly more likely than those with flu to have an underlying chronic respiratory condition (60.2% vs. 40.1%, P < .001) and to be immunocompromised (35% vs. 26.2%, P = .02). Very few of the patients overall (39 patients, 6.3%) were considered young and healthy prior to hospitalization; and significantly fewer of these were in the RSV group than in the influenza group (9 patients and 30 patients, respectively).

Airway obstruction at the time of diagnosis was significantly more common in the RSV patients than in influenza patients (49.5% vs. 39.5%, P = .01), but influenza patients were significantly more likely to have acute respiratory distress syndrome at the time of diagnosis (21.7% vs. 14.6%, P = .02). Rates of coinfections were similar between the groups, and approximately 60% of coinfected patients received at least 72 hours of therapeutic antibiotics. Overall length of hospital stay, ICU stay, and duration of mechanical ventilation were similar between the groups.

The results show that severe RSV occurs mainly in older patients with comorbidities, and these results reflect data from previous studies, the researchers wrote in their discussion. In addition, “patients with influenza infection were significantly more likely to have fever, myalgia, increased CPK level, thrombocytopenia and transaminitis at diagnosis than were those with RSV infection. Whether these differences may be used to guide patient management remains to be determined.”

The study findings were limited by several factors including the retrospective design, and testing for respiratory viruses on symptomatic patients only, rather than all ICU patients, the researchers noted. Other limitations include the inability to show a causal link between viral infections and patient outcomes and the heterogenous management of patients among different centers.

However, the results were strengthened by the large sample size and multivariate analysis, and support the need for interventions to prevent and treat severe RSV, they concluded.

The study received no outside funding. Lead author Dr. Coussement disclosed serving on advisory board for Sanofi.

Hospitalized intensive care patients with respiratory syncytial virus were significantly more likely to be immunocompromised and to have chronic respiratory conditions than those with influenza infections, but in-hospital mortality rates were similar, based on data from 618 adults.

Respiratory syncytial virus is common in adults, but characteristics of RSV patients requiring ICU care have not been explored, despite routine testing for RSV in critically ill patients in many institutions, Julien Coussement, PhD, of Université Libre de Bruxelles, Brussels, and colleagues wrote.

“Influenza is another respiratory virus routinely tested for in ICU patients with respiratory symptoms because of its well-known morbidity and mortality, but there are no data specifically comparing RSV and influenza infections in adult ICU patients,” they noted.

In a retrospective, multicenter study published in the journal CHEST, the researchers analyzed data from 309 adult ICU patients with RSV infection and 309 with influenza infection between November 2011 and April 2018 from 17 sites in France and Belgium. Each RSV patient was matched to a flu patient according to institution and date of diagnosis.

The primary objective was a comparison of in-hospital mortality between the groups, defined as death from any cause during an index hospital stay in acute care. Secondary objectives were comparisons of the clinical and biological characteristics of patients with RSV versus flu.

Overall, in-hospital mortality was not significantly different between the RSV and influenza groups (23.9% vs. 25.6%, P = .63).

However, patients with RSV infection were significantly more likely than those with flu to have an underlying chronic respiratory condition (60.2% vs. 40.1%, P < .001) and to be immunocompromised (35% vs. 26.2%, P = .02). Very few of the patients overall (39 patients, 6.3%) were considered young and healthy prior to hospitalization; and significantly fewer of these were in the RSV group than in the influenza group (9 patients and 30 patients, respectively).

Airway obstruction at the time of diagnosis was significantly more common in the RSV patients than in influenza patients (49.5% vs. 39.5%, P = .01), but influenza patients were significantly more likely to have acute respiratory distress syndrome at the time of diagnosis (21.7% vs. 14.6%, P = .02). Rates of coinfections were similar between the groups, and approximately 60% of coinfected patients received at least 72 hours of therapeutic antibiotics. Overall length of hospital stay, ICU stay, and duration of mechanical ventilation were similar between the groups.

The results show that severe RSV occurs mainly in older patients with comorbidities, and these results reflect data from previous studies, the researchers wrote in their discussion. In addition, “patients with influenza infection were significantly more likely to have fever, myalgia, increased CPK level, thrombocytopenia and transaminitis at diagnosis than were those with RSV infection. Whether these differences may be used to guide patient management remains to be determined.”

The study findings were limited by several factors including the retrospective design, and testing for respiratory viruses on symptomatic patients only, rather than all ICU patients, the researchers noted. Other limitations include the inability to show a causal link between viral infections and patient outcomes and the heterogenous management of patients among different centers.

However, the results were strengthened by the large sample size and multivariate analysis, and support the need for interventions to prevent and treat severe RSV, they concluded.

The study received no outside funding. Lead author Dr. Coussement disclosed serving on advisory board for Sanofi.

Hospitalized intensive care patients with respiratory syncytial virus were significantly more likely to be immunocompromised and to have chronic respiratory conditions than those with influenza infections, but in-hospital mortality rates were similar, based on data from 618 adults.

Respiratory syncytial virus is common in adults, but characteristics of RSV patients requiring ICU care have not been explored, despite routine testing for RSV in critically ill patients in many institutions, Julien Coussement, PhD, of Université Libre de Bruxelles, Brussels, and colleagues wrote.

“Influenza is another respiratory virus routinely tested for in ICU patients with respiratory symptoms because of its well-known morbidity and mortality, but there are no data specifically comparing RSV and influenza infections in adult ICU patients,” they noted.

In a retrospective, multicenter study published in the journal CHEST, the researchers analyzed data from 309 adult ICU patients with RSV infection and 309 with influenza infection between November 2011 and April 2018 from 17 sites in France and Belgium. Each RSV patient was matched to a flu patient according to institution and date of diagnosis.

The primary objective was a comparison of in-hospital mortality between the groups, defined as death from any cause during an index hospital stay in acute care. Secondary objectives were comparisons of the clinical and biological characteristics of patients with RSV versus flu.

Overall, in-hospital mortality was not significantly different between the RSV and influenza groups (23.9% vs. 25.6%, P = .63).

However, patients with RSV infection were significantly more likely than those with flu to have an underlying chronic respiratory condition (60.2% vs. 40.1%, P < .001) and to be immunocompromised (35% vs. 26.2%, P = .02). Very few of the patients overall (39 patients, 6.3%) were considered young and healthy prior to hospitalization; and significantly fewer of these were in the RSV group than in the influenza group (9 patients and 30 patients, respectively).

Airway obstruction at the time of diagnosis was significantly more common in the RSV patients than in influenza patients (49.5% vs. 39.5%, P = .01), but influenza patients were significantly more likely to have acute respiratory distress syndrome at the time of diagnosis (21.7% vs. 14.6%, P = .02). Rates of coinfections were similar between the groups, and approximately 60% of coinfected patients received at least 72 hours of therapeutic antibiotics. Overall length of hospital stay, ICU stay, and duration of mechanical ventilation were similar between the groups.

The results show that severe RSV occurs mainly in older patients with comorbidities, and these results reflect data from previous studies, the researchers wrote in their discussion. In addition, “patients with influenza infection were significantly more likely to have fever, myalgia, increased CPK level, thrombocytopenia and transaminitis at diagnosis than were those with RSV infection. Whether these differences may be used to guide patient management remains to be determined.”

The study findings were limited by several factors including the retrospective design, and testing for respiratory viruses on symptomatic patients only, rather than all ICU patients, the researchers noted. Other limitations include the inability to show a causal link between viral infections and patient outcomes and the heterogenous management of patients among different centers.

However, the results were strengthened by the large sample size and multivariate analysis, and support the need for interventions to prevent and treat severe RSV, they concluded.

The study received no outside funding. Lead author Dr. Coussement disclosed serving on advisory board for Sanofi.