Infection-triggered perturbation of the immune system could induce psychopathology, and psychiatric sequelae were observed after previous coronavirus outbreaks. The spreading of the Severe Acute Respiratory Syndrome Coronavirus (COVID-19) pandemic could be associated with psychiatric implications. We investigated the psychopathological impact of COVID-19 in survivors, also considering the effect of clinical and inflammatory predictors. We screened for psychiatric symptoms 402 adults surviving COVID-19 (265 male, mean age 58), at one month follow-up after hospital treatment. A clinical interview and a battery of self-report questionnaires were used to investigate post-traumatic stress disorder (PTSD), depression, anxiety, insomnia, and obsessive-compulsive (OC) symptomatology. We collected sociodemographic information, clinical data, baseline inflammatory markers and follow-up oxygen saturation levels. A significant proportion of patients self-rated in the psychopathological range: 28% for PTSD, 31% for depression, 42% for anxiety, 20% for OC symptoms, and 40% for insomnia. Overall, 56% scored in the pathological range in at least one clinical dimension. Despite significantly lower levels of baseline inflammatory markers, females suffered more for both anxiety and depression. Patients with a positive previous psychiatric diagnosis showed increased scores on most psychopathological measures, with similar baseline inflammation. Baseline systemic immune-inflammation index (SII), which reflects the immune response and systemic inflammation based on peripheral lymphocyte, neutrophil, and platelet counts, positively associated with scores of depression and anxiety at follow-up. PTSD, major depression, and anxiety, are all high-burden non-communicable conditions associated with years of life lived with disability. Considering the alarming impact of COVID-19 infection on mental health, the current insights on inflammation in psychiatry, and the present observation of worse inflammation leading to worse depression, we recommend to assess psychopathology of COVID-19 survivors and to deepen research on inflammatory biomarkers, in order to diagnose and treat emergent psychiatric conditions.

Anxiety and depression in COVID-19 survivors: Role of inflammatory and clinical predictors.

Importance Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing human coronavirus disease 2019 (COVID-19), which has now spread into a worldwide pandemic. The pulmonary manifestations of COVID-19 have been well described in the literature. Two similar human coronaviruses that cause Middle East respiratory syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV-1) are known to cause disease in the central and peripheral nervous systems. Emerging evidence suggests COVID-19 has neurologic consequences as well. Observations This review serves to summarize available information regarding coronaviruses in the nervous system, identify the potential tissue targets and routes of entry of SARS-CoV-2 into the central nervous system, and describe the range of clinical neurological complications that have been reported thus far in COVID-19 and their potential pathogenesis. Viral neuroinvasion may be achieved by several routes, including transsynaptic transfer across infected neurons, entry via the olfactory nerve, infection of vascular endothelium, or leukocyte migration across the blood-brain barrier. The most common neurologic complaints in COVID-19 are anosmia, ageusia, and headache, but other diseases, such as stroke, impairment of consciousness, seizure, and encephalopathy, have also been reported. Conclusions and Relevance Recognition and understanding of the range of neurological disorders associated with COVID-19 may lead to improved clinical outcomes and better treatment algorithms. Further neuropathological studies will be crucial to understanding the pathogenesis of the disease in the central nervous system, and longitudinal neurologic and cognitive assessment of individuals after recovery from COVID-19 will be crucial to understand the natural history of COVID-19 in the central nervous system and monitor for any long-term neurologic sequelae.

/pdf/neuropathogenesis-and-neurologic-manifestations-of-the-3nzi2nu9la.pdf

Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review.

This prospective nonrandomized open-label cohort study addresses the safety and efficacy of exosomes (ExoFlo™) derived from allogeneic bone marrow mesenchymal stem cells as treatment for severe COVID-19. During April 2020, ExoFlo was provided to 24 SARS-CoV-2 polymerase chain reaction-positive patients at a single hospital center, all of whom met criteria for severe COVID-19 as well as moderate-to-severe acute respiratory distress syndrome. Patients received a single 15 mL intravenous dose of ExoFlo and were evaluated for both safety and efficacy from days 1 to 14 post-treatment. All safety endpoints were met with no adverse events observed within 72 h of ExoFlo administration. A survival rate of 83% was observed. In total, 17 of 24 (71%) patients recovered, 3 of 24 (13%) patients remained critically ill though stable, and 4 of 24 (16%) patients expired for reasons unrelated to the treatment. Overall, after one treatment, patients' clinical status and oxygenation improved with an average pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) increase of 192% (P < 0.001). Laboratory values revealed significant improvements in absolute neutrophil count [mean reduction 32% (P value <0.001)] and lymphopenia with average CD3+, CD4+, and CD8+ lymphocyte counts increasing by 46% (P < 0.05), 45% (P < 0.05), and 46% (P < 0.001), respectively. Likewise, acute phase reactants declined, with mean C-reactive protein, ferritin, and D-dimer reduction of 77% (P < 0.001), 43% (P < 0.001), and 42% (P < 0.05), respectively. In conclusion, owing to its safety profile, capacity to restore oxygenation, downregulate cytokine storm, and reconstitute immunity, ExoFlo is a promising therapeutic candidate for severe COVID-19. Future randomized controlled trials (RCTs) are needed to determine ExoFlo therapeutic potential.

Exosomes Derived from Bone Marrow Mesenchymal Stem Cells as Treatment for Severe COVID-19.

Within two decades, there have emerged three highly pathogenic and deadly human coronaviruses, namely SARS-CoV, MERS-CoV and SARS-CoV-2. The economic burden and health threats caused by these coronaviruses are extremely dreadful and getting more serious as the increasing number of global infections and attributed deaths of SARS-CoV-2 and MERS-CoV. Unfortunately, specific medical countermeasures for these hCoVs remain absent. Moreover, the fast spread of misinformation about the ongoing SARS-CoV-2 pandemic uniquely places the virus alongside an annoying infodemic and causes unnecessary worldwide panic. SARS-CoV-2 shares many similarities with SARS-CoV and MERS-CoV, certainly, obvious differences exist as well. Lessons learnt from SARS-CoV and MERS-CoV, timely updated information of SARS-CoV-2 and MERS-CoV, and summarized specific knowledge of these hCoVs are extremely invaluable for effectively and efficiently contain the outbreak of SARS-CoV-2 and MERS-CoV. By gaining a deeper understanding of hCoVs and the illnesses caused by them, we can bridge knowledge gaps, provide cultural weapons for fighting and controling the spread of MERS-CoV and SARS-CoV-2, and prepare effective and robust defense lines against hCoVs that may emerge or reemerge in the future. To this end, the state-of-the-art knowledge and comparing the biological features of these lethal hCoVs and the clinical characteristics of illnesses caused by them are systematically summarized in the review.

/pdf/from-sars-and-mers-to-covid-19-a-brief-summary-and-1zb6awuduf.pdf

From SARS and MERS to COVID-19: a brief summary and comparison of severe acute respiratory infections caused by three highly pathogenic human coronaviruses.

COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons.

The pathogenesis and treatment of the `Cytokine Storm' in COVID-19.

At present, the global COVID‐19 epidemic has not been completely controlled, and epidemic prevention and control still face severe challenges. As there is no specific treatment for COVID‐19, promoting roll‐out vaccinations and building herd immunity are still the most effective and economic measures to control the COVID‐19 pandemic. However, the neutralizing antibody level in the recipients decreases with time, and the vaccine's protective efficacy gradually weakens. It is still inconclusive whether it is necessary to carry out booster vaccination to strengthen the immune barrier to infection. In this paper, we combined the existing data on the effectiveness and persistence of COVID‐19 vaccines. We found that it is necessary to carry out a booster vaccination strategy. However, not all subjects need to receive one more dose of vaccine 6 months after the initial immunization. Priority should be given to the high‐risk groups, such as the elderly and people with immunodeficiency. A heterologous booster can induce higher immune responses and enhance immune protection than homologous vaccinations. However, more scientific data and clinical studies are needed to verify the safety of heterologous vaccination strategies.

Booster vaccination strategy: Necessity, immunization objectives, immunization strategy, and safety

http://www.journalofinfection.com/article/S0163445322000068/pdf

Incident changes in the prevalence of respiratory virus among children during COVID-19 pandemic in Hangzhou, China

The novel coronavirus 2019 (COVID‐19) caused by SARS‐CoV‐2 spread rapidly worldwide, posing a severe threat to public life and health. It is significant to realize rapid testing and timely control of epidemic situations under the condition of limited resources. However, laboratory‐based standardized nucleic acid detection methods have a long turnaround time and high cost, so it is urgent to develop convenient methods for detecting COVID‐19. This paper summarizes the point‐of‐care testing (POCT) developed for novel coronavirus from three aspects: nucleic acid extraction, nucleic acid amplification, and detection methods. This paper introduces a commercial real‐time detection system that integrates the abovementioned three steps and the matters needing attention in use. The primary purpose of this review is to provide a reference for emergency response and rapid deployment of COVID‐19 and some other emerging infectious diseases.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jmv.27617

Recent advances and clinical application in point‐of‐care testing of SARS‐CoV‐2

https://doi.org/10.1016/j.micinf.2022.104945

Jianhua Mao

Papers

The pathogenesis and treatment of the `Cytokine Storm' in COVID-19.

Booster vaccination strategy: Necessity, immunization objectives, immunization strategy, and safety

Incident changes in the prevalence of respiratory virus among children during COVID-19 pandemic in Hangzhou, China

Recent advances and clinical application in point‐of‐care testing of SARS‐CoV‐2

Application experience of a rapid nucleic acid detection system for COVID-19