Jared Kaltwasser

Common risk factors such as nursing home residence and age increase the likelihood of negative outcomes when a hospitalized patient has 

, but other, less-well-known factors can also have a major impact on the course of a patient’s disease, according to a new analysis.

Those risk factors have been used to create a risk calculator which can help clinicians better understand which patients have a higher likelihood of progression once admitted to the hospital with COVID-19.

The report came from investigators at Johns Hopkins University, including corresponding author Brian T. Garibaldi, MD, PhD. It was 

The data were based on 839 patients who were admitted to 5 hospitals in Maryland and Washington, DC in March and April of this year. The majority of patients (694; 83%) survived their bouts with the disease, and after evaluating the cases of those who survived and those who succumbed, the investigators found patients’ risk factors for severe disease or death varied dramatically from as high as 90% to as low as 5%.

The median age of the patients was 64, and they were split roughly evenly by gender (47% women). The majority of patients were in minority demographic groups that have been shown to be at higher risk of severe disease; 40% were black and 16% were Latinx. However, Garibaldi and colleagues said they did not find a race-based correlation with severity in this data set after adjusting for clinical factors. One in 5 patients (21%) were residents of a nursing home. Half of the nursing home residents admitted to the 5 hospitals ended up dying from the disease.

Forty-five patients already had severe disease when they were admitted to the hospital. Among the other 787, 15% had developed severe disease or died within 12 hours. By the fourth day, 31% had progressed to severe disease or death. The median time from admission to severe disease or death was 1.1 days.

Garibaldi and colleagues said a number of factors correlated with risk of severe disease or death. They included age, nursing home residence, 

, respiratory symptoms, respiratory rate, fever, absolute lymphocyte count, hypoalbuminemia, troponin level, and C-reactive protein level.

, which is available for free on the university’s website and can be used to assess a particular patient’s risk of progression to severe disease or death.

The number of deaths in the study was insufficient to create a similar calculator focused on risk of death specifically, however, the authors cited a number of risk factors, the biggest of which was death. 

Those ages 75 and above had an adjusted hazard ratio of death of 3.56 (95% CI). Living in a nursing home affected risk of death, though the effect only statistically significant if the patient was under age 75 (2.30 HR versus 1.42 HR). Charlson Comorbidity Index scores and Sao2/Fio2 ratios of less than 375 aso lowered a patient’s risk of survival.

Garibaldi and colleagues noted a number of insights from the data. For one, they said strategies to help prevent infection in nursing homes are critical to reducing the number of deaths caused by the illness. They also noted that 1 in 5 patients who died had do not resuscitate/do not intubate orders, which affected the interventions used in those cases.

As for their calculator, the authors said the tool is most effective at predicting progression to severe disease or death in the first 2 days of hospital admission, but they said longitudinal data could be added to the model to strengthen its predictive power at later days.

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Patients who are at highest risk of progression to severe COVID-19 are older patients, those with comorbidities, and those living in nursing homes.

COVID-19 Risk Calculator Helps Predict Which Hospitalized Patients at Highest Risk

New results suggest antibody cocktails might have the power to protect against or treat coronavirus disease 2019 (COVID-19).

The study, based on tests on Syrian hamster models, offers a potentially fruitful avenue to combat the ongoing pandemic, and could potentially help scientists and public health officials buy time until a 

Investigators including corresponding author David Veesler, PhD, of the University of Washington, explained that the virus that causes COVID-19, SARS-CoV-2 attaches to the viral transmembrane spike (S) glycoprotein via a receptor-binding motif (RBM) to angiotensin-converting enzyme 2 (ACE2). Thus, SARS-CoV-2 S is the primary target of vaccine and other therapeutic efforts, Veesler and colleagues noted. However, it’s unclear when a vaccine will be available, leaving a gap for other strategies, such as neutralizing antibodies, they said.

“Prophylactic and/or therapeutic antiviral drugs could address the gap before safe and efficient vaccines become widely available and will continue to have utility in unvaccinated individuals or those who respond poorly to vaccination,” they wrote.

The investigators have already identified a monoclonal antibody (mAb) isolated from the memory B cells of a patient who survived Severe Acute Respiratory Syndrome (SARS) a decade ago which appears to be effective at neutralizing SARS-CoV-2. The mAb works by recognizing the S receptor-binding domain of the virus without blocking attachment of ACE2, the investigators explained. They said RBD-targeted neutralizing antibodies from recovering COVID-19 patients have been shown to provide protection against SARS-CoV-2 challenge in animal models, making RBD an important target of neutralizing Abs. They added that clinical evaluation of therapeutic Abs that interfere with ACE2 binding is currently ongoing.

“mAbs with exceptionally high neutralizing potency, along with distinct and complementary mechanisms of action compared to existing mAbs may enable the formulation of mAb cocktails with enhanced efficacy to control the spread of the virus and prevent resistance,” they wrote.

Based on those emerging insights, the authors set out to discover whether the combination of 2 ultrapotent neutralizing antibodies, subbed S2E12 and S2M11 might successfully partner to fight the virus. Those antibodies were identified after screening more than 800 antibodies from 12 COVID-19 survivors.

In challenge tests using hamsters, the cocktail proved effective. The mAbs were administered via intraperitoneal injection 2 days prior to intranasal challenge with SARS-CoV-2. Four days after that, the investigators examined the lungs of the hamsters to quantify viral RNA and infectious virus. Either antibody alone or cocktails of the two both cut the amount of viral RNA by 2 to 5 orders of magnitude, the authors reported, demonstrating a “remarkable protective efficacy.”

“Cryo-electron microscopy structures show that S2E12 and S2M11 competitively block ACE2 attachment and that S2M11 also locks the spike in a closed conformation by recognition of a quaternary epitope spanning two adjacent receptor-binding domains,” they wrote.

Further study will be needed to see if the results can be replicated in humans, and it is 

not yet clear how long antibody-based resistance would last

. Veesler and colleagues said the success of the cocktail strategy is predicated on its ability to take advantage of multiple effects simultaneously.

“We propose that combinations of mAbs leveraging multiple distinct mechanisms of action with additive or synergistic effects could provide additional benefits for clinical application,” they concluded.

New research based on animal models suggests cocktails of ultrapotent antibodies might help protect patients against SARS-CoV-2.

Antibody Cocktails Could Provide New Prophylactic, Therapeutic Options for COVID-19

A new hookworm vaccine candidate appears to show promise at preventing an affliction affecting nearly half a billion people around the world.

Hookworms can penetrate the skin through soil contaminated by human feces. The larvae then travel to the small intestine, where they feed on blood, resulting in losses of blood and iron. The infection is primarily a problem in low- and middle-income countries, though it is 

. At present, the primary method of counteracting the problem is through mass administration of benzimidazole anthelmintics. That strategy has significant limitations; it does not cure everyone with the infection, and those who are cured can rapidly be re-infected.

 for fighting the problem, an international team of investigators, including corresponding author David J. Diemert, MD, of the George Washington University School of Medicine and Health Sciences, tested a new vaccine candidate against hookworm. The results of the phase I trial were published in 

The vaccine consists of 2 necator antigens, as preclinical studies have suggested a single antigen would not be sufficient. In the current study, the authors evaluated 

-GST-1). Their hope was that these antigens would induce neutralizing antibodies that would interfere with the functions of native proteins and lead to parasite death or an interruption of transmission.

The authors then enrolled 32 adults living in Gabon between the ages of 18 and 50. The patients were randomly assigned into one of 3 groups. Two groups were based on dosage; one group received doses of 30 μg of the experimental vaccines, and the other group received a 100 μg dose. The third group was the control group. Injections were administered intramuscularly, at days 0, 28, and 180. As this was a phase I study, the primary endpoint was safety and the secondary endpoint was immunogenicity.

The vaccine was well-tolerated, with the most common adverse events being mild-to-moderate injection-site pain, headache, myalgia, and nausea. IgG antibodies were induced for each of the vaccine antigens, and the authors reported that mean IgG levels increased with each successive dose.

The higher vaccination dose consistently induced seroconversion, and peak IgG responses were observed 2 weeks following the final vaccine administration. At follow-up 6 months after the last vaccine administration, IgG levels had steadily declined, though the authors said the 100 μg group still had IgG levels significantly higher than baseline at that point.

“Co-administration of these candidate hookworm vaccines was safe and well tolerated, and antigen-specific IgG antibodies were induced to both vaccine antigens,” the authors concluded, noting that this is believed to be the first-ever phase 1 trial of 2 novel hookworm vaccines in sub-Saharan Africa.

The authors noted one limitation: it’s possible that patients enrolled in the study had false-negatives when initially screened for intestinal helminths. If so, it could have distorted the comparison of antibody levels.

However, the authors said the results of the phase I trial are promising. They plan to continue research with a study of the vaccines in healthy children in Gabon and a phase 2 vaccine-challenge study in the United States using a human hookworm infection model.

An estimated 450 million people suffer from hookworm infection each year, but a new study suggests it may soon be possible to vaccinate against the infection.

Hookworm Vaccine Candidate Clears Phase I Hurdles

A new study of teenagers and young adults living with HIV found they are more likely to make healthy lifestyle choices when intervention counseling is delivered in a clinic setting, rather than a community setting.

, found young people living with HIV had higher viral loads when their counseling was delivered at home.

Investigators from several universities wanted to gauge the effectiveness of the Healthy Choices 

 program in differing settings. Healthy Choices is built around 4 30-minute sessions, in which the subjects are counseled on medication adherence and alcohol-related behaviors. The sessions, delivered by trained community health workers over the course of 10 weeks, were designed to leverage motivational language and professional feedback to help the young adults with HIV learn to make choices that will lead them to improved outcomes over time.

In the first session, the study enrollees were asked which behavior — medications or drinking – they wanted to discuss first. A strategy was then developed, and rolled out beginning with the second session.

In the study, the investigators wanted to know whether it made a difference if those sessions took place within a health clinic or at the youth’s home. To find out, they randomized 183 people living with HIV in 5 US cities into 2 groups, one of which received in-home services and the other of which received clinic-based services. The enrollees 

. The study’s endpoints were viral load levels and alcohol usage after 1 year.

The study found both groups had a decline in viral load following the intervention. At 16 weeks, 21% in the home-intervention cohort had an undetectable viral load. That number increased to 22% at 28 weeks, before dropping slightly to 20% at 52 weeks. In the group receiving services in the clinic, 24% had an undetectable viral load at 16 weeks; however, by 28 weeks that number had jumped to 39%, before leveling off to 35% at 52 weeks.

Patients receiving in-clinic interventions had similarly better scores in terms of alcohol usage, which was quantified using the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST).

The authors drew several conclusions from the data. Since at-home and community-based approaches did not achieve superior results, the authors suggested that videoconferencing and mobile apps might be useful alternatives to evaluate for future interventions.

Still, corresponding author Sylvie Naar, PhD, of Florida State University, and colleagues, noted that more than half of the patients in both groups did not achieve viral suppression.

“However, youths who still have unsuppressed viral load in the current era of simplified regimens and effectiveness of antiretroviral therapy, even with less-than-perfect adherence, may be faced with many more psychosocial barriers than youths who struggled with viral suppression a decade ago,” Naar and colleagues wrote.

They said the results of the intervention could therefore have significant public health implications even if they fail to achieve optimal results for more than half of the patient group.

Naar and colleagues concluded by stating there is not a “one-size-fits-all” solution to the problem.

“While brief interventions may be more easily implemented in clinic settings, a more intensive intervention may be needed to sufficiently halt viral replication among youths at highest risk,” Some youths may benefit from motivational interviewing alone, and some may benefit more from motivational interviewing combined with cognitive-behavioral skills-building interventions.”

A new study that compared the results of a behavior intervention program for young adults living with HIV found outcomes were better when the intervention occurred in a clinic rather than at the patients’ homes.

Author | Jared Kaltwasser

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