March 5, 2021 I Repurposed arthritis drug falls short in Phase 3 clinical trial, optimal timing for donating convalescent plasma is within 60 days of symptom onset, most pregnant women and mothers report that they will vaccinate themselves and children, and only small percentage of COVID-19 patients suffer stroke, risk increases with age and CV risk factors. Plus: Clinicians warn of delayed injection-site reaction to Moderna vaccine for proper management and swollen salivary glands may be a common COVID-19 side effect.

Research News

In a letter published in The New England Journal of Medicine, Massachusetts General Hospital researchers call for a greater awareness and communication regarding a delayed injection-site reaction that can occur in some patients who have received the Moderna COVID-19 vaccine. The authors say that large, red, sometimes raised, itchy or painful skin reactions may appear in a small subset of individuals, and clinicians may not be prepared to recognize them and guide patients on treatment options and completion of the second dose of the vaccine. The researchers note that their own clinical observations of the delayed, large, local reactions to the Moderna vaccine, and report a series of 12 patients with the reactions. Symptom onset ranged from four days after the first dose up to 11 days post-vaccination, and most patients were treated with ice and antihistamines or corticosteroids. The study’s authors urge that their immediate goal is to make physicians aware of this possible delayed reaction, so they are not alarmed, but instead well-informed to appropriately treat these patients and not prevent them from receiving the second dose of the vaccine. DOI:10.1056/NEJMc2102131

Less than two% of patients diagnosed with COVID-19 suffered an ischemic stroke, but those who did had a higher risk of requiring long-term care after hospital discharge, a new study published in Stroke has found. University of Missouri School of Medicine researchers teamed up with the MU Institute for Data Science and Informatics and the Tiger Institute for Health Innovation to review data from 54 health care facilities. Out of nearly 28,000 emergency department records, they found 103 patients (1.3%) developed ischemic stroke among 8,163 patients with COVID-19. In comparison, 199 patients (1.0%) developed stroke among 19,513 patients who did not have COVID-19. The researchers found that patients with COVID-19 who developed acute ischemic stoke were older in age, more likely to be Black, and had a higher incidence of cardiovascular risk factors. The mean age of COVID-19 patients with stroke was 68.8 years compared to 54.4 years for those without stroke. Among those patients with COVID-19 and stroke, 45% were Black and 84% had hypertension. The researchers highlight that these findings differ from earlier studies that suggested patients with COVID-19 who developed stroke were younger and without preexisting cardiovascular risk factors. DOI:10.1161/STROKEAHA.120.031786

SARS-CoV-2 may target the oral cavity, finds a new study published in the Journal of Dental Research. Researchers in Italy profiled the oral involvement in 122 recovered COVID-19 patients who were hospitalized and followed up at a single referral visit after a median 104 days from hospital discharge. The researchers found that oral manifestations and, specifically, salivary gland ectasia were common, being detectable in 83.9% and 43% of recovered COVID-19 patients, respectively. Salivary glands were defined as being ectasic when they appeared swollen, with a patent duct and no pus leaking, and this reflected the hyperinflammatory response to SARS-CoV-2, as demonstrated by the significant relationship with C-reactive protein and lactate dehydrogenase (LDH) levels at hospital admission. Temporomandibular joint abnormalities, facial pain, and masticatory muscle weakness were also common. The researchers say that further research is needed to better understand this connection between COVID-19 infection and oral disorders. DOI:10.1177/0022034521997112

Most pregnant women and mothers of children younger than 18 years old say they would receive a COVID-19 vaccine and vaccinate their children, according to a global survey conducted by Harvard T.H. Chan School of Public Health researchers. The survey included nearly 18,000 women across 16 countries who responded to questions about a hypothetical safe and free COVID-19 vaccine with 90% efficacy. Overall, 52% of pregnant women and 73% of non-pregnant women said they would receive the vaccine. 69% of all women surveyed reported that they would vaccinate their children. Vaccine acceptance was the highest in India, the Philippines, and all sampled countries in Latin American, and it was the lowest in Russia, the United States, and Australia. Pregnant women who were hesitant to receive a COVID-19 vaccine said they had concerns about exposing their developing baby to possible harmful side effects, the vaccine being rushed for political reasons, and the lack of safety and effectiveness data in pregnant women. These results are published in the European Journal of Epidemiology. DOI:10.1007/s10654-021-00728-6

Individuals taking statins to lower cholesterol were approximately 50% less likely to die when hospitalized for COVID-19, finds a new study published in Nature Communications. Authors of the study analyzed the outcomes of 2,626 patients with COVID-19 who were admitted to a quaternary academic medical center in Manhattan during the first 18 weeks of the pandemic and compared 648 patients who regularly used statins prior to infection with COVID-19 to 648 patients who did not use statins. Patients in each group were matched based on demographics, comorbidities, and use of other medications at home. The researchers found that 14.8% of the statin users died in the hospital within 30 days of admission compared with 26.5% of patients who did not use statins. The patients on statins also tended to have lower levels of C-reactive protein, an inflammatory marker. DOI:10.1038/s41467-021-21553-1

Israel’s Clalit Research Institute, in collaboration with Harvard University researchers, has published the first large-scale peer-reviewed study on the real-world effectiveness of the Pfizer-BioNTech COVID-19 vaccine in The New England Journal of Medicine. The study took place from December 20, 2020, the launch of Israel’s national vaccination drive, to February 1, 2021. The researchers reviewed data from over 596,000 vaccinated individuals and carefully matched those individuals with the same number of unvaccinated individuals based on an extensive set of factors associated with risk of infection. They determined that in fully vaccinated individuals (7 or more days after the second dose of vaccine), the risk of symptomatic COVID-19 decreased by 94% compared with the unvaccinated, and the risk of severe disease decreased by 92%. In the period immediately preceding the second dose (days 14-20 after the first dose), the risk of symptomatic COVID-19 decreased by 57% in the vaccinated individuals and the risk of severe disease decreased by 62%. DOI:10.1056/NEJMoa2101765

The optimal timeframe for donating convalescent plasma for COVID-19 immunotherapy is within 60 days of symptom onset, say Penn State researchers. Their study, published in Communications Biology, examined the titers of IgM, IgG, and virus neutralizing (VN) antibodies in a cohort of 175 convalescent plasma donors for 142 days after the patients’ symptoms began. They determined that IgM and IgG antibodies persisted in the participants for at least 140 days, however, VN antibodies declined rapidly after 60 days to below the recommended level for convalescent plasma donation. The researchers explain that the levels of VN antibodies are the best possible metric for choosing potential donors for immunotherapy because they provide the most protective immunity. They suggest that once potential donors are identified, those individuals should donate quickly before their valuable VN antibodies begin to decline. DOI:10.1038/s42003-021-01813-y

Abnormal sodium levels in hospitalized COVID-19 patients may predict a higher risk of death or respiratory failure, according to a new study published in the Journal of Clinical Endocrinology & Metabolism. Researchers analyzed the outcomes of 488 adults with COVID-19 admitted to two London hospitals over an eight-week time period in 2020. They found that nearly 32% of those patients with low sodium levels at admission required intubation and mechanical ventilation or oxygen support, compared to only 17.5% of those patients with normal sodium values. Among patients with high sodium levels, nearly 56% died versus approximately 21% of patients who maintained normal sodium levels. The researchers stress the importance of treating abnormal sodium values and avoiding dehydration during hospital admission for COVID-19. DOI:10.1210/clinem/dgab107

Results of a Phase 3 clinical trial found that tocilizumab, a repurposed arthritis drug, did not significantly improve clinical status or mortality rate at 28 days for patients with severe COVID-19 pneumonia who received it compared to a placebo. The clinical trial began in April 2020 and was conducted in 62 hospitals in nine countries, involving 452 patients with confirmed cases of severe COVID-19 pneumonia, randomized into a group of 294 patients who received an intravenous infusion of tocilizumab and 144 patients who received a placebo. Researchers report that they found no reduced mortality rate associated with the drug, however, they did see an improvement in length of stay of eight days with tocilizumab compared to placebo and fewer days on mechanical ventilation. They caution that these secondary outcomes would require subsequent studies to confirm these benefits. These results are published in The New England Journal of Medicine. DOI:10.1056/NEJMoa2028700

In a study published in JAMA, researchers compared characteristics and outcomes of U.S. children and adolescents with Multisystem Inflammatory Syndrome in Children (MIS-C) to patients with severe acute COVID-19 to distinguish patterns of clinical presentation and organ involvement of these patients. The study included 539 patients with MIS-C and 577 patients with severe COVID-19 who were hospitalized between March and October 2020 at 66 U.S. hospitals across 31 states. Researchers determined that patients with MIS-C were more likely than those with severe COVID-19 to be 6 to 12 years old, be non-Hispanic Black, and have severe cardiovascular or mucocutaneous involvement with more extreme inflammation. Those patients with MIS-C also had higher neutrophil to lymphocyte ratios, higher C-reactive protein levels, and lower platelet counts than young patients with severe COVID-19 infection. The researchers hope that these findings can help clinicians differentiate between MIS-C and COVID-19. DOI:10.1001/jamaoto.2020.5698

Industry News

ObvioHealth announced the launch of a hybrid clinical trial for the treatment of COVID-19, using an innovative study design with digital data capture to remotely monitor patient vitals. The U.S. Phase 2/3 study will examine the safety and efficacy of RedHill BioPharma’s RHB-107 (upamostat), using ObvioHealth’s clinical trial ecosystem, including digital devices, a patient-centric smartphone application and home healthcare visits. Upamostat is a novel, orally-administered serine protease inhibitor with antiviral and potential tissue-protective effects which targets human cells rather than the virus itself and is expected to be effective against new viral strains. The Phase 2/3 study is enrolling more than 300 patients with symptomatic COVID-19 who do not require hospital care. Press Release

PatientPop introduced its COVID-19 Vaccine Scheduler and Communication Solution for private healthcare practices. With this all-in-one platform, practices can easily communicate their COVID-19 vaccine plans and availability to patients, schedule vaccine appointments, digitally register and pre-screen patients, and deliver a convenient patient experience. The COVID-19-specific solution includes search-optimized website content, vaccine-specific patient communication, pre-vaccination screening forms, appointment confirmations and reminders, and the ability to send post-appointment satisfaction surveys to patients. Press Release

University of Ottawa and Bruyere Research Institute investigators have been awarded $3.5 million in funding from the Government of Canada’s COVID-19 Immunity Task Force for studies on the effects of COVID-19 on long-term care residents. They will study the immune response of workers and residents in long-term care homes across Ontario, Quebec, and British Columbia over the course of one year. The team will recruit over 3,500 residents and 2,500 workers from these long-term care facilities and collect blood samples over several months. Their goal is to gain insight into how various immunity factors, such as antibodies, react to COVID-19 and vaccines. Press Release

New forecasts on the impact of vaccines and variants on the U.S. COVID-19 trajectory over the next few weeks have been published in a report summary released by Lehigh University researchers. A consensus of 91 forecasters predicts that the B.1.1.7 variant will be found in 42% of all genetic sequences with an S-gene mutation in the first two weeks of March and in 72% in all sequences between March 29 and April 4, 2021. The consensus among experts in the modeling of infectious disease and trained forecasters from Metaculus, is that by the end of February, 55,420,000 people will have received at least one dose of a COVID-19 vaccine. Preliminary data from the Centers for Disease Control (CDC) shows that 49,772,180 people have received an initial dose on February 28, 2021. Consensus forecasts from both Metaculus and Good Judgement Open predicted a decrease in the rate of cases, deaths, and hospitalizations for the last week of February. The researchers say the goal of the report is to support public health officials and the general public. Report

The Food and Drug Administration (FDA) has outlined new guidance for modifying COVID-19 vaccines against viral variants. The agency states that it expects trials for modified vaccines will take approximately two to three months and consist of a few hundred individuals. These new recommendations replace the guidance of the same name issued in October 2020. It encourages vaccine-makers to include both non-vaccinated participants and those previously vaccinated with the authorized vaccine in trials for amended Emergency Use Authorizations (EUAs). Press Release

George Washington University (GW) announced its participation in the Sanofi COVID-19 vaccine clinical trial. The university was selected as one of approximately 25 sites in the United States to launch a phase 2 study for its adjuvanted recombinant protein-based COVID-19 vaccine candidate. The vaccine, developed in partnership with GlaxoSmithKline, uses the same technology as Sanofi’s recombinant influenza vaccine and is similar in design to the newest shingles and hepatitis B vaccines. GW will recruit 40 volunteers for the trial, and all will receive two doses of the vaccine, though certain groups will receive higher or lower amounts of the vaccine. If results are positive, a phase 3 study to evaluate vaccine efficacy could begin as soon as the second quarter of 2021. Press Release