Multifaceted Efforts from Basic Research to Clinical Practice in Controlling COVID-19 Disease

The value of D-dimer assessments in ICU patients with COVID-19 for the prediction of pulmonary embolism (PE) is unclear. The present study had two purposes: 1. To assess the specificity of elevated absolute D-dimer values for PE on admission to the ICU. 2. To assess the specificity of a D-dimer increment for the development of PE during an ICU stay. D-dimer values were paired with the results of a CT pulmonary angiogram (CTPA) and compared in patients with and without PE on admission. In patients without PE on initial imaging and available repeat CTPA during an ICU stay, D-dimer increments between initial and repeat imaging of patients developing PE during an ICU stay were compared with those with persistently no PE. On admission, D-dimers in patients with PE were higher than those in patients without PE (median 850 vs. 6060 μg/L; p < 0.0001). Using a cut-off of 9000 μg/L, the specificity for predicting PE was 100% (CI 95.3–100%). Delta D-dimer during an ICU stay was greater in patients with PE (median 7983 vs. 3815 μg/L; p < 0.005). Using a cut-off of 8000 μg/L, specificity was 100% (CI 79.4–100%). Strongly elevated D-dimer values on admission and marked increases in D-dimer during ICU stays have a high specificity for predicting pulmonary embolism in critically ill COVID-19 patients. Full article

We present the results of a randomized, double-blind, placebo-controlled, multi-center clinical trial phase I/II of the tolerability, safety, and immunogenicity of the inactivated whole virion concentrated purified coronavirus vaccine CoviVac in volunteers aged 18–60 and open multi-center comparative phase IIb clinical trial in volunteers aged 60 years and older. The safety of the vaccine was assessed in 400 volunteers in the 18–60 age cohort who received two doses of the vaccine (n = 300) or placebo (n = 100) and in 200 volunteers in 60+ age cohort all of whom received three doses of the vaccine. The studied vaccine has shown good tolerability and safety. No deaths, serious adverse events (AEs), or other significant AEs related to vaccination have been detected. The most common AE in vaccinated participants was pain at the injection site (p < 0.05). Immunogenicity assessment in stage 3 of Phase II was performed on 167 volunteers (122 vaccinated and 45 in Placebo Group) separately for the participants who were anti-SARS-CoV-2 nAB negative (69/122 in Vaccine Group and 28/45 in Placebo Group) or positive (53/122 in Vaccine Group and 17/45 in Placebo Group) at screening. On Day 42 after the 1st vaccination, the seroconversion rate in participants who were seronegative at screening was 86.9%, with the average geometric mean neutralizing antibody (nAB) titer of 1:20. A statistically significant (p < 0.05) increase in IFN-γ production by peptide-stimulated T-cells was observed at Days 14 and 21 after the 1st vaccination. In participants who were seropositive at screening but had nAB titers below 1:256, the rate of fourfold increase in nAB levels was 85.2%, while in the participants with nAB titers > 1:256, the rate of fourfold increase in nAB levels was below 45%; the participants who were seropositive at screening of the 2nd vaccination did not lead to a significant increase in nAB titers. In conclusion, inactivated vaccine CoviVac has shown good tolerability and safety, with over 85% NT seroconversion rates after complete vaccination course in participants who were seronegative at screening in both age groups: 18–60 and 60+. In participants who were seropositive at screening and had nAB titers below 1:256, a single vaccination led to a fourfold increase in nAB levels in 85.2% of cases. These findings indicate that CoviVac can be successfully used both for primary vaccination in a two-dose regimen and for booster vaccination as a single dose in individuals with reduced neutralizing antibody levels. Full article

The COVID-19 pandemic necessitated sensitive, fast, and inexpensive testing for the virus in 2020 prior to the widespread availability of vaccines. Early testing efforts were limited by bottlenecks on reagents, low-throughput testing options, and the slow return of test results. In this paper, we detail the testing pipeline we established at the University of Wisconsin-Madison for rapid, inexpensive, and sensitive surveillance testing for SARS-CoV-2, and we highlight the strengths of the platform that would allow it to be applied to other disease surveillance projects, SARS-CoV-2 variant testing, or future pandemics. This pipeline can be quickly established for further accreditation and clinical application. Full article

Heart transplantation is a treatment of choice for patients with severe heart failure. Infection transmission from a donor to a recipient remains a prominent problem in organ transplantation. However, the risk of SARS-CoV-2 transmission in nonlung organ transplantation is still unclear. In this article we presented a case of a 28-year-old pregnant woman who developed heart failure soon after recovery from a SARS-CoV-2 infection in the third trimester of gestation. In the postpartum period, the heart disease worsened and the patient required cardiac transplantation. We examined the recipient’s heart and made a diagnosis of left ventricular noncompaction cardiomyopathy. Immunohistochemical analysis showed SARS-CoV-2 antigen expression in the donor’s heart before transplantation, and after the transplantation, an endomyocardial biopsy was taken. Moreover, an ultrastructural assessment of the endomyocardial specimen revealed endothelial and pericyte injury and a single particle on the surface of the endothelium consistent with SARS-CoV-2 viral particles. Recent findings in the literature associated these damages with SARS-CoV-2 infection. The present study describes the rare case of SARS-CoV-2 transmission from donor to postpartum recipient through a heart transplant and demonstrates the importance of endomyocardial biopsy before and after heart transplantation. Full article

Background: Olfactory dysfunction (OD) is a common neurosensory manifestation in long COVID. An effective and safe treatment against COVID-19-related OD is needed. Methods: This pilot trial recruited long COVID patients with persistent OD. Participants were randomly assigned to receive short-course (14 days) oral vitamin A (VitA; 25,000 IU per day) and aerosolised diffuser olfactory training (OT) thrice daily (combination), OT alone (standard care), or observation (control) for 4 weeks. The primary outcome was differences in olfactory function by butanol threshold tests (BTT) between baseline and end-of-treatment. Secondary outcomes included smell identification tests (SIT), structural MRI brain, and serial seed-based functional connectivity (FC) analyses in the olfactory cortical network by resting-state functional MRI (rs–fMRI). Results: A total of 24 participants were randomly assigned to receive either combination treatment (n = 10), standard care (n = 9), or control (n = 5). Median OD duration was 157 days (IQR 127–175). Mean baseline BTT score was 2.3 (SD 1.1). At end-of-treatment, mean BTT scores were significantly higher for the combination group than control (p < 0.001, MD = 4.4, 95% CI 1.7 to 7.2) and standard care (p = 0.009) groups. Interval SIT scores increased significantly (p = 0.009) in the combination group. rs–fMRI showed significantly higher FC in the combination group when compared to other groups. At end-of-treatment, positive correlations were found in the increased FC at left inferior frontal gyrus and clinically significant improvements in measured BTT (r = 0.858, p < 0.001) and SIT (r = 0.548, p = 0.042) scores for the combination group. Conclusions: Short-course oral VitA and aerosolised diffuser OT was effective as a combination treatment for persistent OD in long COVID. Full article

Concentration and memory impairment (named “brain fog”) represents a frequent and disabling neuropsychological sequela in post-acute COVID-19 syndrome (PACS) patients. The aim of this study was to assess whether neurocognitive function could improve after a multidisciplinary rehabilitation program enhanced with individualized neuropsychological treatment. A prospective monocentric registry of PACS patients consecutively admitted to our Rehabilitation Unit was created. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive impairment at admission and discharge. A total of sixty-four (64) PACS patients, fifty-six (56) of them with brain fog, were treated with a day-by-day individualized psychological intervention of cognitive stimulation (45 min) on top of a standard in-hospital rehabilitation program. The mean duration of the acute-phase hospitalization was 55.8 ± 25.8 days and the mean in-hospital rehabilitation duration was 30 ± 10 days. The mean age of the patients was 67.3 ± 10.4 years, 66% of them were male, none had a previous diagnosis of dementia, and 66% of the entire sample had experienced severe COVID-19. At admission, only 12% of the patients had normal cognitive function, while 57% showed mild, 28% moderate, and 3% severe cognitive impairment. After psychological treatment, a significant improvement in the MoCA score was found (20.4 ± 5 vs. 24.7 ± 3.7; p < 0.0001) as a result of significant amelioration in the following domains: attention task (p = 0.014), abstract reasoning (p = 0.003), language repetition (p = 0.002), memory recall (p < 0.0001), orientation (p < 0.0001), and visuospatial abilities (p < 0.0001). Moreover, the improvement remained significant after multivariate analysis adjusted for several confounding factors. Finally, at discharge, 43% of the patients with cognitive impairment normalized their cognitive function, while 4.7% were discharged with residual moderate cognitive impairment. In conclusion, our study provides evidence of the effects of multidisciplinary rehabilitation enhanced with neuropsychological treatment on improvement in the cognitive function of post-acute COVID-19 patients. Full article

The question of COVID-19 and long-COVID-19 course in children remains unsolved. This infection in children, which is associated with COVID-19, can vary from asymptomatic to systemic damage of various systems. Multisystem inflammatory syndrome in children, associated with SARS-CoV-2 (MIS-C), is a serious condition in children and adolescents after experiencing COVID-19. Published data on MIS-C have indicated that the inflammation can be registered in the gastrointestinal tract (60–100%), as well as in cardiovascular (80%), nervous (29–58%), and respiratory (21–65%) systems. However, with the changing characteristics of SARS-CoV-2, the manifestations of COVID-19 and long-COVID-19 in children have also been changing. Currently, there is no clear understanding of the development of severe COVID-19 and MIS-C in children, especially after being exposed to patients with COVID-19. We presented two new clinical courses of multisystem inflammatory syndrome in children with severe multisystem damage after close contact to relatives with COVID-19 or long-COVID-19. Thus, high-risk children, who are positive for SARS-CoV-2 infection after contact with COVID-19 patients, should be clinically managed during the first few months. The identification of the disease complexity requires the involvement of neurologists, cardiologists, and other specialists. Full article