The coronavirus disease 2019 (COVID-19) pandemic began in January 2020 in Wuhan, China, with a new coronavirus designated SARS-CoV-2. The principal cause of death from COVID-19 disease quickly emerged as acute respiratory distress syndrome (ARDS). A key ARDS pathogenic mechanism is the “Cytokine Storm”, which is a dramatic increase in inflammatory cytokines in the blood. In the last two years of the pandemic, a new pathology has emerged in some COVID-19 survivors, in which a variety of long-term symptoms occur, a condition called post-acute sequelae of COVID-19 (PASC) or “Long COVID”. Therefore, there is an urgent need to better understand the mechanisms of the virus. The spike protein on the surface of the virus is composed of joined S1–S2 subunits. Upon S1 binding to the ACE2 receptor on human cells, the S1 subunit is cleaved and the S2 subunit mediates the entry of the virus. The S1 protein is then released into the blood, which might be one of the pivotal triggers for the initiation and/or perpetuation of the cytokine storm. In this study, we tested the hypothesis that the S1 spike protein is sufficient to activate inflammatory signaling and cytokine production, independent of the virus. Our data support a possible role for the S1 spike protein in the activation of inflammatory signaling and cytokine production in human lung and intestinal epithelial cells in culture. These data support a potential role for the SARS-CoV-2 S1 spike protein in COVID-19 pathogenesis and PASC.

Objective: To explore the safety and efficacy of fish oil to modulate parameters of inflammation and immunosenescence in HIV-infected older adults. Design: This study uses a randomized, controlled, double-blind clinical trial. Setting: The study was conducted in an outpatient HIV/AIDS clinic in a large urban Midwestern city in the United States. Subjects: A total of 37 clinically stable HIV-infected adults between the ages of 40 and 70 years of age participated. Interventions: Fish oil 1.6 g/day was administered for 12 weeks or placebo. Outcome measures: Inflammatory cytokine production, surface markers of immunosenescence, and adverse events were measured. Results: After 12 weeks of supplementation, there were no significant differences between the treatment and control groups on any measures of inflammation or immunosenescence in both CD4⁺ and CD8⁺ T lymphocytes. More participants in the treatment group reported adverse gastrointestinal events compared with the control group. Conclusions: A 12-week supplementation regimen of 1.6 g/day of fish oil did not favorably modulate parameters of inflammation or immune senescence in HIV-infected adults. Future studies should test agents that directly target mechanisms that underlie HIV-related inflammation to determine whether reducing inflammation can reverse immunosenescence.

The Coronavirus disease 2019 (COVID-19) pandemic began in Jan. 2020 in Wuhan, China with a new coronavirus designated SARS-CoV-2. The principle cause of death from COVID-19 disease quickly emerged as Acute Respiratory Distress Syndrome (ARDS). A key ARDS pathogenic mechanism is the “Cytokine Storm”. This is a dramatic increase in the blood of inflammatory cytokines. In the last 2 years of the pandemic new pathology has emerged in COVID-19 survivors in which a variety of long-term symptoms emerge. This condition is called “Long COVID”. The spike protein on the surface of the virus (target for the new mRNA/DNA vaccines) is composed of joined S1-S2 subunits. Upon S1 bind-ing to the human ACE2 receptor on cells, the S1 subunit is cleaved and the S2 subunit me-diates entry of the virus. The S1 protein is then released into the blood, which might be one of the pivotal triggers for initiation and/or perpetuation of the cytokine storm. In this study, we tested the hypothesis that the spike S1 protein may activate inflammatory sig-naling and cytokine production independent of the virus. Our data support a potential role for spike S1 activation of inflammatory signaling and cytokine production in human lung and intestinal epithelial cells in culture. These data support a potential role for the SARS-CoV-2 spike S1 protein in COVID-19 pathogenesis.

DSPN is a common manifestation of HIV infection and/or its treatment that can have adverse effects on quality of life and functional status. The pathogenesis remains unclear but likely involves the elaboration of neurotoxic inflammatory cytokines and their metabolites. DSPN is often refractory to available pharmacological treatments, although new treatments involving NGF hold promise for effecting sustained symptom relief and reversing axonal degeneration. Further research is needed to determine the efficacy of nonpharmacological treatments, such as cognitive-behavioral therapies, to alleviate DSPN-associated pain.

Background. HIV infection is associated with systemic inflammation that can increase risk for cardiovascular events. Acupuncture has been shown to have immunomodulatory effects and to improve symptoms in persons with inflammatory conditions.Objective. To test the anti-inflammatory effects of an acupuncture protocol that targets the cholinergic anti-inflammatory pathway (CAIP), a neural mechanism whose activation has been shown to reduce the release of proinflammatory cytokines, in persons with HIV-associated inflammation.Design, Setting, Participants, and Interventions. Double-blind, placebo-controlled clinical trial conducted in an outpatient clinic located in a medically underserved urban neighborhood. Twenty-five clinically-stable HIV-infected persons on antiretroviral therapy were randomized to receive once weekly CAIP-based acupuncture or sham acupuncture.Main Outcome Measures. Outcomes included plasma concentrations of high sensitivity C-reactive protein and D-dimer and fasting lipids.Results. Twenty-five participants completed the protocol (treatment groupn=12, control groupn=13). No adverse events related to the acupuncture protocol were observed. Compared to baseline values, the two groups did not significantly differ in any outcome measures at the end of the acupuncture protocol.Conclusions. CAIP-based acupuncture did not favorably modulate inflammatory or lipid parameters. Additional studies are warranted of CAIP-based protocols of different frequencies/durations.