The associations between longitudinal dynamics and the breadth of SARS-CoV-2 neutralizing antibody (nAb) response with various Long COVID phenotypes before vaccination are not known. The capacity of antibodies to cross-neutralize a variety of viral variants may be associated with ongoing pathology and persistent symptoms. We measured longitudinal neutralizing and cross-neutralizing antibody responses to pre- and post-SARS-CoV-2 Omicron variants in participants infected early in the COVID-19 pandemic, before widespread rollout of SARS-CoV-2 vaccines. Cross-sectional regression models adjusted for clinical covariates and longitudinal mixed-effects models were used to determine the impact of the breadth and rate of decay of neutralizing responses on the development of Long COVID symptoms, as well as Long COVID phenotypes. We identified several novel relationships between SARS-CoV-2 antibody neutralization and the presence of Long COVID symptoms. Specifically, we show that, although nAb responses to the original, infecting strain of SARS-CoV-2 were not associated with Long COVID in cross-sectional analyses, cross-neutralization ID50 levels to the Omicron BA.5 variant approximately 4 months following acute infection was independently and significantly associated with greater odds of Long COVID and with persistent gastrointestinal and neurological symptoms. Longitudinal modeling demonstrated significant associations in the overall levels and rates of decay of neutralization capacity with Long COVID phenotypes. A higher proportion of participants had antibodies capable of neutralizing Omicron BA.5 compared with BA.1 or XBB.1.5 variants. Our findings suggest that relationships between various immune responses and Long COVID are likely complex but may involve the breadth of antibody neutralization responses.

Inflammation is at the core of many chronic conditions and exacerbates infectious conditions, including the severity of coronavirus disease 2019 (COVID-19) infections.
This study aimed to examine the effects of a novel food supplement, palmitoylethanolamide (PEA), specifically Levagen+, as compared with a placebo on proinflammatory biomarkers in adults recently diagnosed with COVID-19 who were unvaccinated and nonhospitalized.
This study was a double-blind randomized placebo-controlled trial conducted October 2020-March 2021 (clinicaltrials.gov: NCT04912921). Participants aged 19-53 y were unvaccinated and recently infected with COVID-19 as indicated by a positive test result per RT-PCR or antigen test, and they reported to the test site following diagnosis as allowed by the CDC\'s return-to-work policy. Participants were stratified by age, sex, and BMI and randomly assigned by coin toss to receive 600 mg Levagen+ twice daily (LEV) or placebo tablets twice daily (CON) for 4 wk. At baseline and week 4, participants completed health histories, 24-h dietary recalls, anthropometrics, and nonfasting blood sampling. The primary outcomes were the 4-wk change between groups for IL-6, C-reactive protein, ferritin, intercellular adhesion molecule 1, soluble P-selectin (sP-selectin), and neutrophil/lymphocyte ratio. Multiple linear regression models were utilized to assess treatment effects on outcomes, adjusting for covariates.
A total of 60 participants completed the study (LEV: n = 30; CON: n = 30). After 4 wk of supplementation, sP-selectin (β = -11.5; 95% CI: -19.8, -3.15; P = 0.0078), IL-1β (β = -22.9; 95% CI: -42.4, -3.40; P = 0.0222), and IL-2 (β = -1.73; 95% CI: -3.45, -0.065; P = 0.0492) concentrations were significantly reduced in the LEV group compared with the CON group.
Inflammatory mechanisms are crucial to optimal resolution of infectious conditions, yet unchecked secretion of inflammatory mediators can promote the dysregulated immune response implicated in COVID-19 complications. Overall, PEA supplementation produced anti-inflammatory effects in individuals recently diagnosed with COVID-19 who were nonhospitalized.

The latest WHO report determined the increasing diversity within the CoV-2 omicron and its descendent lineages. Some heavily mutated offshoots of BA.5 and BA.2, such as BA.4.6, BF.7, BQ.1.1, and BA.2.75, are responsible for about 20% of infections and are spreading rapidly in multiple countries. It is a sign that Omicron subvariants are now developing a capacity to be more immune escaping and may contribute to a new wave of COVID-19. Covid-19 infections often induce many alterations in human physiological defense and the natural control systems, with exacerbated activation of the inflammatory and homeostatic response, as for any infectious diseases. Severe activation of the early phase of hemostatic components, often occurs, leading to thrombotic complications and often contributing to a lethal outcome selectively in certain populations. Development of autoimmune complications increases the disease burden and lowers its prognosis. While the true mechanism still remains unclear, it is believed to mainly be related to the host autoimmune responses as demonstrated, only in some patients suffering from the presence of autoantibodies that worsens the disease evolution. In fact in some studies the development of autoantibodies to angiotensin converting enzyme 2 (ACE2) was identified, and in other studies autoantibodies, thought to be targeting interferon or binding to annexin A1, or autoantibodies to phospholipids were seen. Moreover, the occurrence of autoimmune heparin induced thrombocytopenia has also been described in infected patients treated with heparin for controlling thrombogenicity. This commentary focuses on the presence of various autoantibodies reported so far in Covid-19 diseases, exploring their association with the disease course and the durability of some related symptoms. Attempts are also made to further analyze the potential mechanism of actions and link the presence of antibodies with pathological complications.

Inflammation is at the core of many chronic conditions and exacerbates infectious conditions, including the severity of coronavirus disease 2019 (COVID-19) infections.
This study aimed to examine the effects of a novel food supplement, palmitoylethanolamide (PEA), specifically Levagen+, as compared with a placebo on proinflammatory biomarkers in adults recently diagnosed with COVID-19 who were unvaccinated and nonhospitalized.
This study was a double-blind randomized placebo-controlled trial conducted October 2020-March 2021 (clinicaltrials.gov: NCT04912921). Participants aged 19-53 y were unvaccinated and recently infected with COVID-19 as indicated by a positive test result per RT-PCR or antigen test, and they reported to the test site following diagnosis as allowed by the CDC\'s return-to-work policy. Participants were stratified by age, sex, and BMI and randomly assigned by coin toss to receive 600 mg Levagen+ twice daily (LEV) or placebo tablets twice daily (CON) for 4 wk. At baseline and week 4, participants completed health histories, 24-h dietary recalls, anthropometrics, and nonfasting blood sampling. The primary outcomes were the 4-wk change between groups for IL-6, C-reactive protein, ferritin, intercellular adhesion molecule 1, soluble P-selectin (sP-selectin), and neutrophil/lymphocyte ratio. Multiple linear regression models were utilized to assess treatment effects on outcomes, adjusting for covariates.
A total of 60 participants completed the study (LEV: n = 30; CON: n = 30). After 4 wk of supplementation, sP-selectin (β = -11.5; 95% CI: -19.8, -3.15; P = 0.0078), IL-1β (β = -22.9; 95% CI: -42.4, -3.40; P = 0.0222), and IL-2 (β = -1.73; 95% CI: -3.45, -0.065; P = 0.0492) concentrations were significantly reduced in the LEV group compared with the CON group.
Inflammatory mechanisms are crucial to optimal resolution of infectious conditions, yet unchecked secretion of inflammatory mediators can promote the dysregulated immune response implicated in COVID-19 complications. Overall, PEA supplementation produced anti-inflammatory effects in individuals recently diagnosed with COVID-19 who were nonhospitalized.

OBJECTIVE: To describe changes in sexually transmitted infection (STI) diagnoses during the first wave of the COVID-19 pandemic in Spain.
METHODS: We collected demographic, chronological, and clinical data for all patients seen for a possible STI at Hospital La Paz, Centro Sanitario Sandaval, and Centro de Diagnóstico Médico in Madrid and Hospital Costa del Sol in Malaga between March 14, 2020 and June 30, 2020.
RESULTS: We identified 674 STI diagnoses. The median age of the patients was 33 years. Most cases were observed among people aged 30 to 40 years and among men who have sex with men. The most common diagnoses were proctitis (36.5%), syphilis (16%), nongonococcal (13.3%) and gonococcal (11.3%) urethritis, genital herpes (8.8%), vulvovaginitis/cervicitis (8.3%), and genital warts (4.2%). A microbiologically confirmed diagnosis was on record for 77% of cases. The main microorganisms identified wereChlamydia trachomatis (35.7%), Neisseria gonorrhoeae (31.4%), and Treponema pallidum (17.2%). The number of STI diagnoses increased after the easing of lockdown restrictions, which resulted in greater freedom of movement and more consultations. On comparing the 2019 and 2020 STI registries from Centro Sanitario Sandoval and Hospital La Paz for the period March to June, we observed reductions (of up to 81%) in all STI diagnoses.
CONCLUSIONS: Physical distancing and movement restrictions appear to have resulted in a reduction in the incidence of STIs, although these measures did not completely eliminate sexual risk behaviors.
OBJECTIVE: Describir los cambios en el comportamiento de las ITS durante la situación de alerta sanitaria por la pandemia SARS-CoV-2.
UNASSIGNED: Se recogieron datos demográficos, cronológicos y clínicos de todos los pacientes que solicitaron atención médica por ITS en los hospitales La Paz y Costa del Sol, y los Centros Sandoval y de Diagnóstico Médico entre el 14/03/2020 y el 30/06/2020.
RESULTS: Documentamos 674 casos de ITS. La mediana de edad fue de 33 años. El mayor porcentaje de casos se dio en el rango de 30-40 años y en hombres que tenían sexo con hombres. Los diagnósticos más frecuentes fueron: proctitis (36,5%), sífilis (16%), uretritis no gonocócica (13,3%) y gonocócica (11,3%), herpes genital (8,8%), vulvovaginitis/cervicitis (8,3%) y condilomas (4,2%).En 77% de los casos hubo confirmación microbiológica, siendo los microorganismos más frecuentes Chlamydia trachomatis (35,7%), Neisseria gonorrhoeae (31,4%) y Treponema pallidum (17,2%).Se constató un incremento del número de casos de ITS tras el desconfinamiento, explicable por las mayores libertades y el aumento de consultas. Comparando los registros de ITS del Centro Sandoval y el Hospital La Paz en los cuatrimestres de marzo a junio de 2019 frente a 2020, se observó una disminución en 2020 de todos los diagnósticos, de hasta un 81% menos que en 2019.
CONCLUSIONS: Las medidas de distanciamiento y limitación de movilidad aparentemente generaron una disminución de la incidencia de ITS, pero sin llegar a una inhibición completa de las conductas sexuales de riesgo.

Post-Traumatic Stress Disorder (PTSD), characterized by re-experiencing, avoidance, negative affect, and impaired memory processing, may develop after traumatic events. PTSD is complicated by impaired plasticity and medial prefrontal cortex (mPFC) activity, hyperactivity of the amygdala, and impaired fear extinction. Cannabidiol (CBD) is a promising candidate for treatment due to its multimodal action that enhances plasticity and calms hyperexcitability. CBD\'s mechanism in the mPFC of PTSD patients has been explored extensively, but literature on the mechanism in the dorsal raphe nucleus (DRN) is lacking. Following the PRISMA guidelines, we examined current literature regarding CBD in PTSD and overlapping symptomologies to propose a mechanism by which CBD treats PTSD via corticoraphe circuit. Acute CBD inhibits excess 5-HT release from DRN to amygdala and releases anandamide (AEA) onto amygdala inputs. By first reducing amygdala and DRN hyperactivity, CBD begins to ameliorate activity disparity between mPFC and amygdala. Chronic CBD recruits the mPFC, creating harmonious corticoraphe signaling. DRN releases enough 5-HT to ameliorate mPFC hypoactivity, while the mPFC continuously excites DRN 5-HT neurons via glutamate. Meanwhile, AEA regulates corticoraphe activity to stabilize signaling. AEA prevents DRN GABAergic interneurons from inhibiting 5-HT release so the DRN can assist the mPFC in overcoming its hypoactivity. DRN-mediated restoration of mPFC activity underlies CBD\'s mechanism on fear extinction and learning of stress coping.

BACKGROUND: Coronavirus Disease 2019 (Covid-19) is expanding worldwide. The characteristics of this infection in patients varies from country to country. To move forward, clinical data on infected patients are needed. Here, we report a comparison between fatalities and recovery of patients with severe Covid-19, based on demographic and clinical characteristics.
METHODS: Between 5 March and 12 May 2020 in Mashhad, Iran, 1278 of 4000 suspected Covid-19 patients were confirmed positive by real-time reverse-transcriptase-polymerase-chain-reaction assay of upper respiratory specimens. We compared the demographic, exposure history and clinical symptoms of 925 survivors and 353 fatal cases with confirmed disease.
RESULTS: Mean (SD) age for all confirmed patients was 56.9 (18.7) years, 67.1 (15.9) years in fatal cases and 53.0 (18.3) years in survivors. Multivariate logistic regression analysis showed that the outcome of patients was associated with age (odds ratio = 1.049, P = 0.0001, 95% CI = 1.040-1.057). Despite a high burden of Covid-19 infections in the 30-39 and 40-49 year age groups, most of these (89.6 and 87.2%, respectively) recovered. The median (IQR) duration of hospitalization was 9.0 (6.0-14.0) days. The most prevalent co-morbidities were cardiovascular disorders (21%) and diabetes (16.3%). Dyspnoea (72.7%), cough (68.1%) and fever (63.8%) were the most frequent clinical symptoms. Healthcare workers, of whom two (3%) died, comprised 5.2% of infected cases. Combination antiviral and antibiotic therapy was used in 43.0% of cases.
CONCLUSIONS: The characteristics of severe Covid-19 varied substantially between fatal cases and survivors, with diabetes and cardiovascular disorders the most prevalent co-morbidities. In contrast to other studies, there were a higher number of fatalities in younger patients in our setting.

BACKGROUND: The consequences of severe acute respiratory syndrome corona virus 2 on mother and fetus remain unknown due to a lack of robust evidence from prospective studies.
OBJECTIVE: This study evaluated the effect of coronavirus disease 2019 (COVID-19) on neonatal outcomes and the scope of vertical transmission.
METHODS: This ambispective observational study enrolled pregnant women with COVID-19 in North India from April 1 to August 31, 2020 to evaluate neonatal outcomes and the risk of vertical transmission.
RESULTS: A total of 44 neonates born to 41 COVID-19-positive mothers were evaluated. Among them, 28 patients (68.3%) (2 sets of twins) were delivered within 7 days of testing positive for COVID-19, 23 patients (56%) (2 sets of twins) were delivered by cesarean section; 13 newborns (29.5%) had low birth weight; 7 (15.9%) were preterm; and 6 (13.6%) required neonatal intensive care unit admission, reflecting an increased incidence of cesarean delivery and low birth weight but zero neonatal mortality. Samples of cord blood, placental membrane, vaginal fluid, amniotic fluid, peritoneal fluid (in case of cesarean section), and breast milk for COVID-19 reverse transcription-polymerase chain reaction tested negative in 22 prospective delivery cases. Nasopharyngeal swabs of 2 newborns tested positive for COVID-19: one at 24 hours and the other on day 4 of life. In the former case, biological samples were not collected as the mother was asymptomatic and her COVID-19 report was available postdelivery; hence, the source of infection remained inconclusive. In the latter case, all samples tested negative, ruling out the possibility of vertical transmission. All neonates remained asymptomatic on follow-up.
CONCLUSIONS: COVID-19 does not have direct adverse effects on the fetus per se. The possibility of vertical transmission is almost negligible, although results from larger trials are required to confirm our findings.

COVID-19 commonly presents with upper respiratory symptoms; however, studies have shown that SARS-CoV-2 infection affects multiple organ systems. Here, we review the pathophysiology and imaging characteristics of SARS-CoV-2 infection in organ systems throughout the body and explore commonalities.
Familiarity with the underlying pathophysiology and imaging characteristics is essential for the radiologist to recognize these findings in patients with COVID-19 infection. Though pulmonary findings are the most prevalent presentation, COVID-19 may have multiple manifestations and recognition of the extrapulmonary manifestations is especially important because of the potential serious and long-term effects of COVID-19 on multiple organ systems.

Coronavirus disease 2019 (COVID-19) is a highly transmissible disease that has affected more than 90% of the countries worldwide. At least 17 million individuals have been infected, and some countries are still battling first or second waves of the pandemic. Nucleic acid tests, especially reverse transcription polymerase chain reaction (RT-PCR), have become the workhorse for early detection of COVID-19 infection. Positive controls for the molecular assays have been developed to validate each test and to provide high accuracy. However, most available positive controls require cold-chain distribution and cannot serve as full-process control. To overcome these shortcomings, we report the production of biomimetic virus-like particles (VLPs) as SARS-CoV-2 positive controls. A SARS-CoV-2 detection module for RT-PCR was encapsidated into VLPs from a bacteriophage and a plant virus. The chimeric VLPs were obtained either by in vivo reconstitution and coexpression of the target detection module and coat proteins or by in vitro assembly of purified detection module RNA sequences and coat proteins. These VLP-based positive controls mimic SARS-CoV-2 packaged ribonucleic acid (RNA) while being noninfectious. Most importantly, we demonstrated that the positive controls are scalable, stable, and can serve broadly as controls, from RNA extraction to PCR in clinical settings.