The Zika virus (ZIKV) gained prominence as a significant global pathogen after the 2015-2016 outbreaks associated it with an increase in neurological complications in adults and congenital malformations. Different mechanisms have been proposed by which ZIKV may cross the blood-brain barrier and reach the central nervous system to cause neuroinflammation. Although ZIKV infection triggers a robust immune response, the virus has developed different strategies to escape it. Furthermore, although the virus is present in areas with cocirculation of other pathogenic agents, few studies have evaluated the cross-immune reactions and coinfection of ZIKV. Coinfections of ZIKV with other viruses, parasites, and bacteria are described. Such interactions can worsen infections and alter the immune response, imposing new therapeutic challenges and highlighting the need for more studies in the field. In this review, we discuss various aspects of ZIKV biology, focusing on the impacts of coinfections.

Climate change and pollution are a major existential threat. Healthcare contributes a noteworthy 4-6% to the total carbon footprint and 5-7% of the total greenhouse gas (GHG) emissions. Environmental pollution and modern lifestyles are also contributing to the increased prevalence of autoimmune and lifestyle-related rheumatic disease. In this review, we assess both the effects of rheumatological practice on climate change and the potential impact of climate change on rheumatological diseases. Preliminary evidence suggests that climate change is linked with the inception or exacerbation of some of the autoimmune and inflammatory rheumatic diseases (AIRDs) like rheumatoid arthritis, lupus, systemic sclerosis, and reactive arthritis. Furthermore, with rampant industrialization and pollution, emerging infections such as Dengue, Zika virus, and chikungunya have emerged as triggers of inflammatory arthritis. Strategies at different levels are proposed to mitigate the effect of the healthcare industry and the community on the environment. The rheumatology community can acknowledge and begin to address the challenges of climate change and health.

The Zika virus (ZIKV) is classified within the Flavivirus genus of the Flaviviridae family and is categorized as an arbovirus. The virus was initially identified in a rhesus monkey in Uganda in 1947 and later in a human in Nigeria in 1952. Since 2007, the prevalence of the virus has been on the rise, culminating in a major outbreak in the United States (US) in 2015. During this outbreak, the adult population was severely impacted, experiencing a range of symptoms, including organ failure, microcephaly, fetal death, and Guillain-Barré syndrome (GBS). Additionally, skin rash, limb swelling, fever, headache, and heightened sensitivity are found in most adults with Zika syndrome. Although the virus can be transmitted through blood, vertical transmission from mother to child, and sexual contact, the primary way of transmission of the virus is through the Aedes mosquito. Cells such as neurons, macrophages, peripheral dendritic cells, and placental cells are among the target cells that the virus can infect. The TAM AXL receptor plays a crucial role in infection. After the virus enters the body through the bloodstream, it spreads in the body with a latent period of 3 to 12 days. Currently, there is no specific treatment or publicly available vaccine for the ZIKV. Limited laboratory testing has been conducted, and existing drugs originally designed for other pathogens have been repurposed for treatment. Given the Aedes mosquito's role as a vector and the wide geographical impact of the virus, this study aims to comprehensively investigate Zika's pathogenesis and clinical symptoms based on existing knowledge and research. By doing so, we seek to enhance our understanding of the virus and inform future prevention and treatment strategies.

Late-onset pain is frequent following COVID-19, and many pathogenetic mechanisms have been proposed. Identifying the main features of patients may help in designing tailored rehabilitative interventions.

We enrolled post-COVID-19 patients with an increase in pain intensity of two points on the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS) at 52 weeks compared to the pre-COVID-19 condition. All subjects were retrospectively monitored at 12, 26, and 52 weeks. A specific pain assessment was performed to determine the characteristics and mechanisms of pain. Catastrophizing, kinesiophobia, and other psychological symptoms were evaluated. The pressure pain threshold (PPT) and temporal summation (TS) were measured and compared in age- and sex-matched healthy controls to analyse pain characteristics.

A total of 67 patients were recruited, with 20 of them presenting an increase in pain at 52 weeks. Subjects of the two subgroups were similar in demographic and clinical characteristics at baseline; significant differences in fatigue, anxiety, mobility, ability to perform daily activities, and general health perception were recorded at 26 weeks. Fatigue significantly predicted pain onset (β = 0.54, p = 0.002). Sixteen different body regions were identified as painful, with a pain intensity of 6.0 ± 1.9. Most of the samples did not show neuropathic or nociplastic mechanisms. No differences in PPT and TS were recorded between patients and healthy controls.

Almost one out of three patients hospitalized for COVID-19 developed pain 1 year later, and fatigue seems responsible for chronicity. An overlapping of conditions may explain late-onset post-COVID-19 pain, and a comprehensive approach must be considered for patient management.

Late-onset pain is frequent in post-COVID-19 syndrome and an overlapping of different mechanisms seems to be responsible for its development. Among many predisposing factors, fatigue in the months before seems to be one of the primary causes of pain one year following infection and its management may help to identify new strategies for prevention and treatment of late-onset pain.

Chikungunya can result in debilitating arthralgia, often presenting as acute, self-limited pain, but occasionally manifesting chronically. Little is known about differences in chikungunya-associated arthralgia comparing children to adults over time. To characterize long-term chikungunya-associated arthralgia, we recruited 770 patients (105 0-4 years old [y/o], 200 5-9 y/o, 307 10-15 y/o, and 158 16+ y/o) with symptomatic chikungunya virus infections in Managua, Nicaragua, during two consecutive chikungunya epidemics (2014-2015). Participants were assessed at ~15 days and 1, 3, 6, 12, and 18 months post-fever onset. Following clinical guidelines, we defined participants by their last reported instance of arthralgia as acute (≤10 days post-fever onset), interim (>10 and <90 days), or chronic (≥90 days) cases. We observed a high prevalence of arthralgia (80-95%) across all ages over the study period. Overall, the odds of acute arthralgia increased in an age-dependent manner, with the lowest odds of arthralgia in the 0-4 y/o group (odds ratio [OR]: 0.27, 95% confidence interval [CI]: 0.14-0.51) and the highest odds of arthralgia in the 16+ y/o participants (OR: 4.91, 95% CI: 1.42-30.95) relative to 10-15 y/o participants. Females had higher odds of acute arthralgia than males (OR: 1.63, 95% CI: 1.01-2.65) across all ages. We found that 23-36% of pediatric and 53% of adult participants reported an instance of post-acute arthralgia. Children exhibited the highest prevalence of post-acute polyarthralgia in their legs, followed by the hands and torso - a pattern not seen among adult participants. Further, we observed pediatric chikungunya presenting in two distinct phases: the acute phase and the subsequent interim/chronic phases. Thus, differences in the presentation of arthralgia were observed across age, sex, and disease phase in this longitudinal chikungunya cohort. Our results elucidate the long-term burden of chikungunya-associated arthralgia among pediatric and adult populations.

The progressive reappearance of Zika virus (ZIKV) infections since October 2013 and its circulation in >70 countries and territories (from French Polynesia to Brazil and other countries in the Americas, with sporadic spread in Europe and the East) has long been reported as a global public health emergency. ZIKV is a virus transmitted by arthropods (arboviruses), mainly by Aedes mosquitoes. ZIKV can also be transmitted to humans through mechanisms other than vector infection such as sexual intercourse, blood transfusions, and mother-to-child transmission. The latter mode of transmission can give rise to a severe clinical form called congenital Zika syndrome (CZS), which can result in spontaneous abortion or serious pathological alterations in the fetus such as microcephaly or neurological and orofacial anomalies. In this study, beside a succinct overview of the etiological, microbiological, and epidemiological aspects and modes of transmission of Zika virus infections, we have focused our attention on the pathogenetic and histopathological aspects in pregnancy and the pathogenetic and molecular mechanisms that can determine microcephaly, and consequently the clinical alterations, typical of the fetus and newborns, in a subject affected by CZS.

Although evaluated within other specialties, physicians' beliefs towards climate change and human health have not been described within Interventional Pain Medicine (IPM). Understanding belief systems is essential for developing solutions to build sustainable practices.

Assess beliefs toward climate change within the field of IPM.

Spine Intervention Society (SIS) members were invited to participate in an anonymous RedCap survey by email, social media, and advertisement at the 2022 SIS Annual Meeting. Descriptive statistics were calculated, and associations were estimated using Chi-Square (significance: p < 0.05).

One hundred and seventy-five participants responded to the survey. Participants most often identified as white (66 %; 95 % CI 57-73 %), male (78 %; 95 % CI 71-84 %), and from the United States (US) (76 %; CI 95 % 58-72 %), with 87 % (n = 123/141; 95 % CI 82-93 %) agreeing that climate change is happening (agree or strongly agree). While 78 % (95 % CI 80-92 %) agree that climate change and sustainability are important to them, only 47 % (95 % CI 34-51 %) agree that these are important to their patients. Those beliefs did not differ by age or geographical area (p > 0.05). However, physicians in non-leadership positions are more likely to disagree or strongly disagree that climate change is important to them (χ2(2) = 15.98; p < 0.05), to their patients (χ2(2) = 17.21; p < 0.05), or that societies should advocate for climate policies (χ2(2) = 9.19; p < 0.05). Non-US physicians were more likely to believe that physicians have responsibilities to bring awareness to the health effects of climate change (χ2(2) = 6.58; p < 0.05) and to agree that climate change is important to their patients (χ2(2) = 10.50; p < 0.05).

Understanding specialty-specific physician views on climate change is essential for developing solutions to reduce the carbon footprint of medical practice and improve sustainability. The majority of SIS members believe that climate change is happening. Non-US physicians and physician-leaders are more likely to believe that climate change impacts their patients and that societies should advocate for climate policies.

Chronic cases of chikungunya fever represent a public health problem in countries where the virus circulates. The disease is prolonged, in some cases, for years, resulting in disabling pain and bone erosion among other bone and joint problems. As time progresses, tissue damage is persistent, although the virus has not been found in blood or joints. The pathogenesis of these conditions has not been fully explained. Additionally, it has been considered that there are multiple factors that might intervene in the viral pathogenesis of the different conditions that develop. Other mechanisms involved in osteoarthritic diseases of non-viral origin could help explain how damage is produced in chronic conditions. The aim of this review is to analyze the molecular and cellular factors that could be involved in the tissue damage generated by different infectious conditions of the chikungunya virus.

Arboviruses target bone forming osteoblasts and perturb bone remodeling via paracrine factors. We previously reported that Zika virus (ZIKV) infection of early-stage human mesenchymal stromal cells (MSCs) inhibited the osteogenic lineage commitment of MSCs. To understand the physiological interplay between bone development and ZIKV pathogenesis, we employed a primary in vitro model to examine the biological responses of MSCs to ZIKV infection at different stages of osteogenesis. Precommitted MSCs were infected at the late stage of osteogenic stimulation (Day 7) with ZIKV (multiplicity of infection of 5). We observe that MSCs infected at the late stage of differentiation are highly susceptible to ZIKV infection similar to previous observations with early stage infected MSCs (Day 0). However, in contrast to ZIKV infection at the early stage of differentiation, infection at a later stage significantly elevates the key osteogenic markers and calcium content. Comparative RNA sequencing (RNA-seq) of early and late stage infected MSCs reveals that ZIKV infection alters the mRNA transcriptome during osteogenic induction of MSCs (1251 genes). ZIKV infection provokes a robust antiviral response at both stages of osteogenic differentiation as reflected by the upregulation of interferon responsive genes (n > 140). ZIKV infection enhances the expression of immune-related genes in early stage MSCs while increasing cell cycle genes in late stage MSCs. Remarkably, ZIKA infection in early stage MSCs also activates lipid metabolism-related pathways. In conclusion, ZIKV infection has differentiation stage-dependent effects on MSCs and this mechanistic understanding may permit the development of new therapeutic or preventative measures for bone-related effects of ZIKV infection.

Introduction: Alphaviruses may cause arthritis, but there is a lack of studies assessing it in flaviviruses such as dengue. Through the 28 Joint Disease Activity Score (DAS-28), incorporating swollen joint counts, and through the Arthritis Index from Western Ontario and McMaster Universities (WOMAC), we assessed pain, stiffness, and dimensions of arthritic function in post-DENV patients. Methods: Prospective study of a cohort of participants who were diagnosed with dengue in centres in Honduras from December 2019 to February 2020, with a follow-up period of 4 months to evaluate post-dengue rheumatological disease through the WOMAC and DAS-28 questionnaires. Results: After a four-month follow-up phase with 281 participants, the final cohort comprised 58.8% women and 41.20% men. After the follow-up, 63.02% persisted with the clinical findings. According to WOMAC, joint involvement was higher in women with (58.76%) (p < 0.0001) these symptoms or functional limitations when performing daily activities were limited to pain when walking (34.81% vs. 5.51%), climbing or descending stairs (36.46% vs. 8.66%), and at night at bedtime (28.73% vs. 7.08%). With the DAS-28, we found at least one alteration with inflammation or pain in 14.91% of the participants, primarily women (p < 0.01). Discussion: Joint involvement was high during the dengue epidemic in 2019. We observed a significant proportion of women with inflammation and joint pain, showing that dengue may lead to the development of chronic rheumatological findings, although lower than in CHIKV, still affecting everyday life and, consequently, their quality of life. Additional long-term evaluation studies after dengue are required.

Although the impact of microbial infections on orthopedic clinical outcomes is well recognized, the influence of viral infections on the musculoskeletal system might have been underestimated.

To systematically review the available evidence on risk factors and musculoskeletal manifestations following viral infections and to propose a pertinent classification scheme.

We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), the Reference Citation Analysis (RCA), and Scopus for completed studies published before January 30, 2021, to evaluate risk factors and bone and joint manifestations of viral infection in animal models and patient registries. Quality assessment was performed using SYRCLE's risk of bias tool for animal studies, Moga score for case series, Wylde score for registry studies, and Newcastle-Ottawa Scale for case-control studies.

Six human and four animal studies were eligible for inclusion in the qualitative synthesis. Hepatitis C virus was implicated in several peri- and post-operative complications in patients without cirrhosis after major orthopedic surgery. Herpes virus may affect the integrity of lumbar discs, whereas Ross River and Chikungunya viruses provoke viral arthritis and bone loss.

Evidence of moderate strength suggested that viruses can cause moderate to severe arthritis and osteitis. Risk factors such as pre-existing rheumatologic disease contributed to higher disease severity and duration of symptoms. Therefore, based on our literature search, the proposed clinical and pathogenetic classification scheme is as follows: (1) Viral infections of bone or joint; (2) Active bone and joint inflammatory diseases secondary to viral infections in other organs or tissues; and (3) Viral infection as a risk factor for post-surgical bacterial infection.

: Coronavirus disease 2019 (COVID-19) causes a long-term and persistent condition with clinical features similar to previous virulent outbreaks and other epidemics. Currently, post-COVID syndrome (PCS) is recognized as a new entity in the context of SARS-CoV-2 infection. Though its pathogenesis is not completely understood, persistent inflammation from acute illness and the development of autoimmunity play a critical role in its development. As the pandemic develops, the increasing latent and overt autoimmunity cases indicate that PCS is at the intersection of autoimmunity.

The mechanisms involved in the emergence of PCS, their similarities with post-viral and post-care syndromes, its inclusion in the spectrum of autoimmunity and possible targets for its treatment.

An autoimmune phenomenon plays a major role in most causative theories explaining PCS. Due to the wide scope of symptoms and pathophysiology associated with PCS, there is a need for both PCS definition and classification criteria (including severity scores). Longitudinal and controlled studies are necessary to better understand this new entity, and to confirm that PCS is the chronic phase of COVID-19 as well as to find what additional factors participate into its development. With the high prevalence of COVID-19 cases worldwide, together with the current evidence on latent autoimmunity in PCS, we may observe an increase of autoimmune diseases (ADs) in the coming years. Vaccination's effect on the development of PCS and ADs will also receive attention in the future. Health and social care services need to develop a new framework to deal with PCS.

COVID-19 is a disease that is challenging science, health-care systems, and humanity. An astonishingly wide spectrum of manifestations of multi-organ damage, including musculoskeletal, can be associated with SARS-CoV-2.

In the acute phase of COVID-19, fatigue, myalgia, and arthralgia are the most common musculoskeletal symptoms.

Post-COVID-19 syndrome is a group of signs and symptoms that are present for >12 weeks. The associated musculoskeletal manifestations are fatigue, arthralgia, myalgia, new-onset back pain, muscle weakness, and poor physical performance.

Data on COVID-19 complications are growing due to large absolute numbers of cases and survivors in these 2 years of the pandemic. Additional musculoskeletal manifestations encountered are falls by the elderly, increased mortality after hip fracture, reduced bone mineral density and osteoporosis, acute sarcopenia, rhabdomyolysis, Guillain-Barré syndrome, muscle denervation atrophy, fibromyalgia, rheumatological disease triggering, septic arthritis, adhesive capsulitis, myositis, critical illness myopathy, onset of latent muscular dystrophy, osteonecrosis, soft-tissue abscess, urticarial vasculitis with musculoskeletal manifestations, and necrotizing autoimmune myositis.

A wide range of signs and symptoms involving the musculoskeletal system that affect quality of life and can result in a decrease in disability-adjusted life years. This powerful and unpredictable disease highlights the importance of multimodality imaging, continuing education, and multidisciplinary team care to support preventive measures, diagnosis, and treatment.

The complexities of dealing with rheumatic diseases in tropical countries are diverse and likely due to limited health care infrastructure, lack of diagnostic and therapeutic facilities, impact of dominant prevailing diseases, and the challenges of differentiating from infectious and non-infectious disease mimics. Several tropical diseases present with musculoskeletal and rheumatic manifestations and often pose a diagnostic dilemma to rheumatologists. The diagnosis is often delayed or the disease is misdiagnosed, leading to poor patient outcomes. Endemic tropical diseases like tuberculosis and leprosy have myriad rheumatic presentations and remain important differentials to consider in patients with rheumatic manifestations. Infection with human immunodeficiency virus is a great masquerade and can mimic manifestations of multiple diseases. The role of viral infections in triggering and perpetuating autoimmunity is well known and chikungunya arthritis is a classic example of the same. This review highlights the rheumatic manifestations of tropical diseases and aims to create awareness among the caregivers. Key Points • It is crucial to be aware and identify infectious diseases presenting with rheumatic manifestations in the tropics. • Presentations akin to classic rheumatic syndromes such as rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus and vasculitis are common.