Long-term complications after infection with SARS-CoV-1, influenza and MERS-CoV - Lessons to learn in long COVID?

The COVID-19 pandemic has affected millions of people worldwide, and while the mortality rate remains the primary concern, it is becoming increasingly apparent that many COVID-19 survivors experience long-term sequelae, representing a major concern for both themselves and healthcare providers. Comparing long-term sequelae following COVID-19 to those of other respiratory viruses such as influenza, MERS-CoV, and SARS-CoV-1 is an essential step toward understanding the extent and impact of these sequelae. A literature search was carried out using the PubMed. database. Search-terms included "persistent", "long-term", "chronic", and MeSH-terms for SARS-CoV-1, MERS-CoV and Influenza. Only English-language articles were selected. Articles were screened by title/abstract and full-text readings. Key points for comparison were persistent symptoms > 4 weeks, virus type, study design, population size, admission status, methods, and findings. Thirty-one articles were included: 19 on SARS-CoV-1, 10 on influenza, and 2 on MERS-CoV-survivors. Damage to the respiratory system was the main long-term manifestation after the acute phase of infection. Quality of life-related and psychological sequelae were the second and third most widely reported symptoms, respectively. Consistent with long-term sequelae from COVID-19, persisting cardiovascular, neurological, musculoskeletal, gastrointestinal impairments were also reported. In summary, the long-term sequelae following COVID-19 are a significant concern, and while long-term sequelae following influenza, MERS-CoV, and SARS-CoV-1 have also been reported, their prevalence and severity are less clear. It is essential to continue to study and monitor the long-term effects of all respiratory viruses so as to improve our understanding and develop strategies for prevention and treatment.

Myopathic changes in patients with long-term fatigue after COVID-19.

OBJECTIVE: To investigate the peripheral nerve and muscle function electrophysiologically in patients with persistent neuromuscular symptoms following Coronavirus disease 2019 (COVID-19). METHODS: Twenty consecutive patients from a Long-term COVID-19 Clinic referred to electrophysiological examination with the suspicion of mono- or polyneuropathy were included. Examinations were performed from 77 to 255 (median: 216) days after acute COVID-19. None of the patients had received treatment at the intensive care unit. Of these, 10 patients were not even hospitalized. Conventional nerve conduction studies (NCS) and quantitative electromyography (qEMG) findings from three muscles were compared with 20 age- and sex-matched healthy controls. RESULTS: qEMG showed myopathic changes in one or more muscles in 11 patients (55%). Motor unit potential duration was shorter in patients compared to healthy controls in biceps brachii (10.02 ± 0.28 vs 11.75 ± 0.21), vastus medialis (10.86 ± 0.37 vs 12.52 ± 0.19) and anterior tibial (11.76 ± 0.31 vs 13.26 ± 0.21) muscles. All patients with myopathic qEMG reported about physical fatigue and 8 patients about myalgia while 3 patients without myopathic changes complained about physical fatigue. CONCLUSIONS: Long-term COVID-19 does not cause large fibre neuropathy, but myopathic changes are seen. SIGNIFICANCE: Myopathy may be an important cause of physical fatigue in long-term COVID-19 even in non-hospitalized patients.

Longitudinal distribution of macroinvertebrates in snowmelt streams in northeast Greenland: understanding biophysical controls.

In a changing climate, Arctic streams are expected to show more influence from snowmelt, rainfall and groundwater, and less domination from glacial meltwater sources. Snowmelt streams are characteristic features of Arctic ecosystems, yet our current understanding of longitudinal patterns in benthic macroinvertebrate assemblages in these systems is limited when compared to glacier-fed systems. This study characterised longitudinal patterns of macroinvertebrate communities in snowmelt streams in northeast Greenland to provide novel insights into Arctic stream communities as dominant water sources shift with climate change. Benthic macroinvertebrates and environmental variables were sampled at three sites along five streams. Taxa diversity, evenness and abundance were expected to increase with distance from the stream source due to enhanced channel stability and warmer water temperature. This expectation for diversity and evenness was found in two streams, but abundance was up to ten times higher at the upstream sites compared to downstream, where biofilm biomass and ionic load were also highest. Here communities were largely dominated by the genus Eukiefferiella (Chironomidae). In the other three streams, no clear pattern in longitudinal macroinvertebrate community composition was evident due to low channel stability along the entire stream length. This study highlights the considerable variation in macroinvertebrate zonal distribution between snowmelt streams in northeast Greenland. A change towards more snowmelt-dominated streams in the Arctic could lead to shifts in the longitudinal organisation of macroinvertebrate community assemblages and the dominant species as a function of channel stability characteristics.

Sequential Vacc-4x and romidepsin during combination antiretroviral therapy (cART): Immune responses to Vacc-4x regions on p24 and changes in HIV reservoirs.

OBJECTIVES: The REDUC clinical study Part B investigated Vacc-4x/rhuGM-CSF therapeutic vaccination prior to HIV latency reversal using romidepsin. The main finding was a statistically significant reduction from baseline in viral reservoir measurements. Here we evaluated HIV-specific functional T-cell responses following Vacc-4x/rhuGM-CSF immunotherapy in relation to virological outcomes on the HIV reservoir. METHODS: This study, conducted in Aarhus, Denmark, enrolled participants (n = 20) with CD4>500 cells/mm3 on cART. Six Vacc-4x (1.2 mg) intradermal immunizations using rhuGM-CSF (60 µg) as adjuvant were followed by 3 weekly intravenous infusions of romidepsin (5 mg/m2). Immune responses were determined by IFN-γ ELISpot, T-cell proliferation to p24 15-mer peptides covering the Vacc-4x region, intracellular cytokine staining (ICS) to the entire HIVGag and viral inhibition. RESULTS: The frequency of participants with CD8+ T-cell proliferation assay positivity was 8/16 (50%) at baseline, 11/15 (73%) post-vaccination, 6/14 (43%) during romidepsin, and 9/15 (60%)post-romidepsin. Participants with CD8+ T-cell proliferation assay positivity post-vaccination showed reductions in total HIV DNA post-vaccination (p = 0.006; q = 0.183), post-latency reversal (p = 0.005; q = 0.183), and CA-RNA reductions post-vaccination (p = 0.015; q = 0.254). Participants (40%) were defined as proliferation 'Responders' having ≥2-fold increase in assay positivity post-baseline. Robust ELISpot baseline responses were found in 87.5% participants. No significant changes were observed in the proportion of polyfunctional CD8+ T-cells to HIVGag by ICS. There was a trend towards increased viral inhibition from baseline to post-vaccination (p = 0.08). CONCLUSIONS: In this 'shock and kill' approach supported by therapeutic vaccination, CD8+ T-cell proliferation represents a valuable means to monitor functional immune responses as part of the path towards functional HIV cure.

Adaptive responses to static conditions in nutrient-rich cultures of luminous Ralstonia eutropha.

The lux-gene fused Ralstonia eutropha, when adapting to static conditions, causes stratification of air-exposed and nutrient-rich cultures at above 0.15 mg biomass ml(-1). The O2 respiring biofilm (luminous neuston) phase, along with the dark sub-neustonic suspension phase, develops within 5-60 min. The instability of the biphasic static culture was identified as a reason for occasionally observable oscillatory bioluminescence.