Computerized Cognitive Testing in Long COVID Patients With Prolonged Symptoms of Brain Fog and Cognitive Impairment

Purpose: To identify cognitive impairments in patients (pts) with long COVID using the Cambridge Brain Sciences (CBS) computerized cognitive test (CCT) commonly used to evaluate cognitive function after concussions and traumatic brain injuries. Method(s): Retrospective review from May 2021-Sept 2022 of 16 (4 male, 12 female) patients with long COVID, ages 13- 66 (avg 46), with average of 10 months from COVID infection to time of evaluation. Cognitive (cog) performance and concussion profile symptom scores were assessed with CBS CCT and the Concussion Clinical Profiles screening tool (CP screen) respectively. Result(s): The total CP symptom score average was 34/89 (ranging 7-68) in the cohort. The predominant profile was cog fatigue scoring (1.8/3) on average. CBS CCT tested cog impairment (CI) and was divided into 5 categories (0-4): no CI, borderline (scores between the 21st-30th percentile), mild (1 test < / = 20th percentile), moderate (2-3 tests < / = 20th percentile), and severe CI (>3 tests,/520th percentile). Data showed 2/16 (13%) patients had no CI, 5/16 (31%) had borderline CI, 5/16 (31%) had mild CI, 3/16 (19%) had moderate CI, and 1/16 (6%) pts had severe CI. Although not significant, there was a positive correlation between CI and cog profile score (P = 0.3149) when performing a linear regression test. Deficits were most common in the CBS CTT composites of grammatical reasoning/verbal processing and attention, with 4/16 patients scoring < 20th percentile for each test. The lowest average percentile scores for the cohort were in visuospatial processing and verbal short-term memory. Conclusion(s): Most long COVID patients assessed with CCT demonstrated signs of CI, in particular in verbal processing and memory, followed by visual processing. In addition to the CCT results illustrating CI, the top CP profile of cognitive fatigue in this cohort suggests that the brain fog experienced by long COVID patients may be quantified. Significance: CCT may be a useful tool in assessing and quantifying those with Long COVID with chronic symptoms of cognitive fog, fatigue, or impairment. Targeted interventions aimed at specific deficits can aid in treatment and recovery.

Age related differences in monocyte subsets, cytokine patterns and the production of anti-SARS- CoV- 2 antibodies during acute COVID-19 -a prospective observational longitudinal study

Background: The COVID-19 pandemic highlighted the vulnerability of the elderly population towards infectious threats, illustrating that aging is accompanied by dysregulated immune responses summarised in terms like inflammaging, immunoparalysis and immunothrombosis. Aim(s): To gain a better understanding on the underlying mechanisms of the age-associated risk of adverse outcome in individuals experiencing a SARS-CoV- 2 infection, we analysed the impact of age on circulating monocyte phenotypes, activation markers, inflammatory cytokines, haemostatic parameters and the onset of anti-SARS- CoV- 2 antibody production in the context of COVID-19 disease progression and outcome. Method(s): Blood samples were collected at the day of hospital admission followed by repeated blood draws (EK1315/2020). Blood parameters were quantified by bead-based immunoassays and flow cytometry. Mixed linear models were applied to explore if the cytokine levels, monocyte subset ratios and antibody titers develop differently over the disease course in younger and elderly COVID-19 patients and whether this development in turn differs between the outcome groups. Result(s): Our data indicate no age-associated differences in monocyte subset composition. However, age and outcome are associated with differences in monocyte activation status. Moreover, a distinct cytokine pattern of IL-6, IL-8 and TNF in elderly survivors versus non-survivors suggests that older patients with adverse outcome experience an inappropriate immune response. Anti-spike S1 IgGs are reduced in elderly. However, deceased patients had higher anti-spike IgG levels than patients requiring intensive care indicating that antibodies are not necessarily protective against adverse outcome. In addition, strong correlations were found between anti-spike S1-, anti-nucleocapsid and anti-RBD IgGs and platelet counts implying that platelets may play an underestimated role in the production of anti-SARS- CoV- 2 antibodies. Conclusion(s): Our study underscores the importance of longitudinal monitoring in elderly COVID-19 patients, as dynamic changes after symptom onset can be observed, which allow for a differentiated insight into confounding factors that impact the complex pathogenesis following an infection with SARS-CoV- 2.

Camostat Mesylate Versus Lopinavir/Ritonavir in Hospitalized Patients With COVID-19-Results From a Randomized, Controlled, Open Label, Platform Trial (ACOVACT).

Background: To date, no oral antiviral drug has proven to be beneficial in hospitalized patients with COVID-19. Methods: In this randomized, controlled, open-label, platform trial, we randomly assigned patients ≥18 years hospitalized with COVID-19 pneumonia to receive either camostat mesylate (CM) (considered standard-of-care) or lopinavir/ritonavir (LPV/RTV). The primary endpoint was time to sustained clinical improvement (≥48 h) of at least one point on the 7-category WHO scale. Secondary endpoints included length of stay (LOS), need for mechanical ventilation (MV) or death, and 29-day mortality. Results: 201 patients were included in the study (101 CM and 100 LPV/RTV) between 20 April 2020 and 14 May 2021. Mean age was 58.7 years, and 67% were male. The median time from symptom onset to randomization was 7 days (IQR 5-9). Patients in the CM group had a significantly shorter time to sustained clinical improvement (HR = 0.67, 95%-CI 0.49-0.90; 9 vs. 11 days, p = 0.008) and demonstrated less progression to MV or death [6/101 (5.9%) vs. 15/100 (15%), p = 0.036] and a shorter LOS (12 vs. 14 days, p = 0.023). A statistically nonsignificant trend toward a lower 29-day mortality in the CM group than the LPV/RTV group [2/101 (2%) vs. 7/100 (7%), p = 0.089] was observed. Conclusion: In patients hospitalized for COVID-19, the use of CM was associated with shorter time to clinical improvement, reduced need for MV or death, and shorter LOS than the use of LPV/RTV. Furthermore, research is needed to confirm the efficacy of CM in larger placebo-controlled trials. Systematic Review Registration: [https://clinicaltrials.gov/ct2/show/NCT04351724, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001302-30/AT], identifier [NCT04351724, EUDRACT-NR: 2020-001302-30].

Establishing Human and Animal Stool Testing for SARS-CoV-2 to Determine Feasibility of Fecal/Oral Transmission

The Current COVID-19 disease pandemic is caused by the Coronavirus SARS-CoV-2. SARS-related viruses in humans are generally carried by animals and human infections are only due to contact with infected animals. But in the case of SARS-CoV-2, human to human transmission is the most studied route of infection and primarily through fomites or respiratory particulates. The objective of this project was to determine feasibility of methods to test and detect infectious SARS-CoV-2 virus and viral RNA in stool. Once detected, the results were used to support the hypothesis that fecal/oral exposure to SARS-CoV2 virus is a potential route of infection in animal models and humans and an area to address in the control and prevention of COVID-19 disease.

An approach to lifting self-isolation for health care workers with prolonged shedding of SARS-CoV-2 RNA.

PURPOSE: According to the European Public Health Authority guidance for ending isolation in the context of COVID-19, a convalescent healthcare worker (HCW) can end their isolation at home and resume work upon clinical improvement and two negative RT-PCR tests from respiratory specimens obtained at 24-h intervals at least 8 days after the onset of symptoms. However, convalescent HCWs may shed SARS-CoV-2 viral RNA for prolonged periods. METHODS: 40 healthy HCWs off work because of ongoing positive RT-PCR results in combined nasopharyngeal (NP) and oropharyngeal (OP) swabs following SARS-CoV-2 infection were invited to participate in this study. These HCWs had been in self-isolation because of a PCR-confirmed SARS-CoV-2 infection. NP and OP swabs as well as a blood sample were collected from each participant. RT-PCR and virus isolation was performed with each swab sample and serum neutralization test as well as two different ELISA tests were performed on all serum samples. RESULTS: No viable virions could be detected in any of 29 nasopharyngeal and 29 oropharyngeal swabs taken from 15 long-time carriers. We found SARSCoV- 2 RNA in 14/29 nasopharyngeal and 10/29 oropharyngeal swabs obtained from screening 15 HCWs with previous COVID-19 up to 55 days after symptom onset. Six (40%) of the 15 initially positive HCWs converted to negative and later reverted to positive again according to their medical records. All but one HCW, a healthy volunteer banned from work, showed the presence of neutralizing antibodies in concomitantly taken blood samples. Late threshold cycle (Ct) values in RT-PCR [mean 37.4; median 37.3; range 30.8-41.7] and the lack of virus growth in cell culture indicate that despite the positive PCR results no infectivity remained. CONCLUSION: We recommend lifting isolation if the RT-PCR Ct-value of a naso- or oropharyngeal swab sample is over 30. Positive results obtained from genes targeted with Ct-values > 30 correspond to non-viable/noninfectious particles that are still detected by RT-PCR. In case of Ct-values lower than 30, a blood sample from the patient should be tested for the presence of neutralizing antibodies. If positive, non-infectiousness can also be assumed.

Late onset pulmonary embolism in young male otherwise healthy COVID-19 patients.

SARS-CoV-2 infection is associated with increased risk of thrombosis in severely ill patients but little is known about the risk in outpatients with mild to moderate disease. Our case series consists of four male otherwise healthy patients between 32 and 50 years of age. Initial symptoms completely resolved but they developed new onset of dyspnea and thoracic pain at days 14 to 26. CT scan revealed pulmonary embolism in all patients which led to hospitalization. Standard anticoagulation practice needs to be re-evaluated and may  be considered for certain outpatients with COVID-19.

Successful management of the first reported case in Austria of COVID-19 with ARDS.

We report the successful management of a patient with severe respiratory failure due to COVID-19 admitted to an intensive care unit complicated by secondary catheter-related infection of Candida glabrata. We are discussing some of the clinical challenges and the pitfalls in molecular diagnosis of SARS-CoV-2, including the fact that a positive PCR result may not always reflect infectiousness.