The novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of coronavirus disease 2019 (COVID-19). Across the globe, a subset of patients who sustain an acute SARS-CoV-2 infection are developing a wide range of persistent symptoms that do not resolve over the course of many months. These patients are being given the diagnosis Long COVID or Post-acute sequelae of COVID-19 (PASC). It is likely that individual patients with a PASC diagnosis have different underlying biological factors driving their symptoms, none of which are mutually exclusive. This paper details mechanisms by which RNA viruses beyond just SARS-CoV-2 have be connected to long-term health consequences. It also reviews literature on acute COVID-19 and other virus-initiated chronic syndromes such as post-Ebola syndrome or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to discuss different scenarios for PASC symptom development. Potential contributors to PASC symptoms include consequences from acute SARS-CoV-2 injury to one or multiple organs, persistent reservoirs of SARS-CoV-2 in certain tissues, re-activation of neurotrophic pathogens such as herpesviruses under conditions of COVID-19 immune dysregulation, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation issues, dysfunctional brainstem/vagus nerve signaling, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage care for specific patients with the diagnosis.

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Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms

Data on the association of human immunodeficiency virus (HIV) infection with adverse outcomes in patients with COVID-19 are conflicting. This systematic review and meta-analysis aimed to summarize the available information on the risk of hospitalization, severe disease, and death attributable to HIV in patients with COVID-19.PubMed, EMBASE, Web of Science, and SCOPUS were searched through October 25, 2021, to identify relevant studies, without language restriction. A random-effects model was used to pool estimates.We included 44 studies reporting information from 38,971,065 patients with COVID-19. The pooled prevalence of HIV among COVID-19 patients was 26.9 ‰ (95% CI 22.7-31.3) and was significantly higher in studies conducted in Africa compared to those conducted elsewhere (118.5‰ [95% CI 84.8-156.9, 11 studies] vs 10.9‰ [95% CI 8.8-13.2, 27 studies]). In pooled analyses of unadjusted odds ratio, HIV-positive individuals were more likely to be admitted to hospital (OR: 1.49; 95% CI 1.01-2.21, 6 studies) compared to HIV-negative individuals. In the adjusted (for age and sex) analyses, HIV was associated with an increased risk of death (hazard ratio: 1.76, 95% CI 1.31-2.35, 2 studies). However, HIV was not associated with the severity of the disease (OR: 1.28; 95% CI 0.77-2.13, 13 studies), or death (OR: 0.81; 95% CI 0.47; 1.41, 23 studies) in patients with COVID-19 in the meta-analysis of unadjusted odds ratio.Our findings suggest that patients with HIV have an increased risk of hospital admission for COVID-19. HIV seems to be independently associated with increased risk of mortality in COVID-19 patient in adjusted analysis. However, this evidence was derived from only two studies. 

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Outcomes of patients with HIV and COVID-19 co-infection: a systematic review and meta-analysis

Data suggest that interleukin (IL)-6 blockade could reduce mortality in severe COVID-19, yet IL-6 is only modestly elevated in most patients. Chen et al. describe the role of soluble interleukin-6 receptor (sIL-6R) in IL-6 trans-signaling, and how understanding the IL-6:sIL-6R axis might help define and treat COVID-19 cytokine storm syndrome.

Soluble Interleukin-6 Receptor in the COVID-19 Cytokine Storm Syndrome.

Thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly (TAFRO) syndrome is a heterogeneous entity manifesting with a constellation of symptoms described above that can occur in the context of idiopathic multicentric Castleman disease (iMCD) as well as infectious diseases, malignancies, and rheumatologic disorders. So, iMCD-TAFRO is an aggressive subtype of iMCD with TAFRO syndrome and often hyper-vascularized lymph nodes. Since we proposed diagnostic criteria of iMCD-TAFRO in 2016, we have accumulated new insights on the disorder and additional cases have been reported worldwide. In this systematic review and cohort analysis, we established and validated a definition for iMCD-TAFRO. First, we searched PubMed and Japan Medical Abstracts Society databases using the keyword "TAFRO" to extract cases. Patients with possible systemic autoimmune diseases and hematologic malignancies were excluded. Our search identified 54 cases from 50 articles. We classified cases into three categories: (1) iMCD-TAFRO (TAFRO syndrome with lymph node histopathology consistent with iMCD), (2) possible iMCD-TAFRO (TAFRO syndrome with no lymph node biopsy performed and no other co-morbidities), and (3) TAFRO without iMCD or other co-morbidities (TAFRO syndrome with lymph node histopathology not consistent with iMCD or other comorbidities). Based on the findings, we propose an international definition requiring four clinical criteria (thrombocytopenia, anasarca, fever/hyperinflammatory status, organomegaly), renal dysfunction or characteristic bone marrow findings, and lymph node features consistent with iMCD. The definition was validated with an external cohort (the ACCELERATE Natural History Registry). The present international definition will facilitate a more precise and comprehensive approach to the diagnosis of iMCD-TAFRO.

Validated international definition of the thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly clinical subtype (TAFRO) of idiopathic multicentric Castleman disease

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The virus primarily affects the lungs where it induces respiratory distress syndrome ranging from mild to acute, however, there is a growing body of evidence supporting its negative effects on other system organs that also carry the ACE2 receptor, such as the placenta. The majority of newborns delivered from SARS-CoV-2 positive mothers test negative following delivery, suggesting that there are protective mechanisms within the placenta. There appears to be a higher incidence of pregnancy-related complications in SARS-CoV-2 positive mothers, such as miscarriage, restricted fetal growth, or still-birth. In this review, we discuss the pathobiology of COVID-19 maternal infection and the potential adverse effects associated with viral infection, and the possibility of transplacental transmission.

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The Effects of COVID-19 on the Placenta During Pregnancy.

COVID-19 cytokine storm syndrome: a threshold concept

Clinical utility of serum IgG4 measurement.

Background: Classroom-based education (CBE) is ubiquitous in postgraduate medical education (PGME), but to date no studies have synthesized the literature on the topic. We conducted a scoping review focusing on academic half days and noon conferences. Methods: We searched 4 databases (MEDLINE [OVID], Embase [OVID], ERIC [EBSCO] and Web of Science) from inception to December 2021, performed reference and citation harvesting, and applied predetermined inclusion and exclusion criteria to our screening. We used 2 frameworks for the analysis: “experiences, trajectories and reifications” and “description, justification and clarification.” Results: We included 90 studies, of which 55 focused on resident experiences, 29 on trajectories and 6 on reification. We classified 44 studies as “description,” 38 as “justification” and 8 as “clarification.” In the description studies, 12 compared academic half days with noon conferences, 23 described specific teaching topics, and 9 focused on resources needed for CBE. Justification studies examined the effects of CBE on outcomes, such as examination scores (17) and use of teaching strategies in team-based learning, principles of adult learning and e-learning (15). Of the 8 clarification studies, topics included the role of CBE in PGME, stakeholder perspectives and transfer of knowledge between classroom and workplace. Interpretation: Much of the existing literature is either a description of various aspects of CBE or justification of particular teaching strategies. Few studies exist on how and why CBE works; future studies should aim to clarify how CBE facilitates resident learning within the sociocultural framework of PGME.

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Tien T.T. Quach

Papers

COVID-19 cytokine storm syndrome: a threshold concept

Clinical utility of serum IgG4 measurement.

Academic half days, noon conferences and classroom-based education in postgraduate medical education: a scoping review