The COVID-19 pandemic has resulted in the loss of millions of lives, although a majority of those infected have managed to survive. Consequently, a set of outcomes, identified as long COVID, is now emerging. While the primary target of SARS-CoV-2 is the respiratory system, the impact of COVID-19 extends to various body parts, including the bone. This study aims to investigate the effects of acute SARS-CoV-2 infection on osteoclastogenesis, utilizing both ancestral and Omicron viral strains. Monocyte-derived macrophages (MDM), which serve as precursors to osteoclasts, were exposed to both viral variants. However, the infection proved abortive, even though ACE2 receptor expression increased post-infection, with no significant impact on cellular viability and redox balance. Both SARS-CoV-2 strains heightened osteoclast formation in a dose-dependent manner, as well as CD51/61 expression and bone resorptive ability. Notably, SARS-CoV-2 induced early pro-inflammatory M1 macrophage polarization, shifting towards an M2-like profile. Osteoclastogenesis-related genes (RANK, NFATc1, DC-STAMP, MMP9) were upregulated, and surprisingly, SARS-CoV-2 variants promoted RANKL-independent osteoclast formation. This thorough investigation illuminates the intricate interplay between SARS-CoV-2 and osteoclast precursors, suggesting potential implications for bone homeostasis and opening new avenues for therapeutic exploration in COVID-19.

Background & Aims: Hepatitis B virus (HBV) can be completely suppressed after antiviral treatment; however, some patients with chronic hepatitis B (CHB) still exhibit elevated alanine aminotransferase (ALT) levels and sustained disease progression. The aim of this study was to provide novel insights into the mechanism and potential predictive biomarkers of persistently elevated ALT (PeALT) in patients with CHB after complete viral inhibition. Methods: CHB Patients with undetectable HBV DNA at least 12 months after antiviral treatment were enrolled from a prospective, observational cohort. Correlations between plasma metabolites and the risk of elevated ALT were examined using multivariate logistic regression. Results: Of the 1238 patients with CHB who achieved complete viral suppression, 40 (3.23%) had PeALT levels during follow-up (median follow-up: 2.42 years). Additionally, 40 patients with persistently normal ALT (PnALT) levels were matched 1:1 as controls. Ser-Phe-Ala (variable importance in projection [VIP] = 4.28), Lys-Ala-Leu-Glu (VIP = 4.49), 3-methylhippuric acid (VIP = 3.04), 3-methylxanthine (VIP = 2.62), and 7-methylxanthine (VIP = 3.35) were identified as critical differential metabolites between the two groups and independently associated with PeALT risk. Ser-Phe-Ala and Lys-Ala-Leu-Glu levels could be used to discriminate patients with PeALT from those with PnALT. Furthermore, N-acetyl-l-methionine (NALM) demonstrated the strongest negative correlation with ALT levels. NALM supplementation alleviated liver injury and hepatic necrosis induced by carbon tetrachloride in mice. Conclusions: Changes in circulating metabolites may contribute to PeALT levels in patients with CHB who have achieved complete viral suppression after antiviral treatment.

We estimated the dynamics of the neutralizing response against XBB sublineages and T cell response in PWH with previous AIDS and/or CD4<200/mm 3 receiving the bivalent original strain/BA.4-5 booster dose (bBD) in fall 2022. Samples were collected before the shot (T0), 15 days (T1), 3 (T3), and 6 months (T6) after. PWH were stratified by immunization status: hybrid immunity (HI; vaccination plus COVID-19) vs. non-hybrid immunity (nHI; vaccination only). At T1, 16% and 30% of PWH were non-responders in terms of anti-XBB.1.16 or anti-EG.5.1 nAbs, respectively. At T3, a significant waning of anti-XBB.1.16, EG.5.1 and -XBB.1 nAbs was observed both in HI and nHI but nAbs in HI were higher than in nHI. At T6 both HI and nHI individuals displayed low mean levels of anti-XBB.1.16 and EG.5.1 nAbs. Regarding T cell response, IFN-γ values were stable over time and similar in HI and nHI. Our data showed that in PLWH, during the prevalent circulation of the XBB.1.16, EG.5.1, and other XBB sublineages, a bBD mRNA vaccine might not confer broad protection against them. With a view to the 2023/2024 vaccination campaign, the use of the monovalent XBB.1.5 mRNA vaccine should be urgently warranted in PWH to provide adequate protection.

A document by Lu Zhang. Click on the document to view its contents.

Mpox is a zoonotic disease historically reported in Africa. Since 2003, limited outbreaks have occurred outside Africa. In 2022, the global spread of cases with sustained interhuman transmission and unusual disease features raised public health concerns. We explore the mpox outbreak in Rio de Janeiro (RJ) state, Brazil, in an observational study of mpox-suspected cases from June to December 2022. Data collection relied on a public healthcare notification form. Diagnosis was determined by MPXV-PCR. In 46 confirmed cases, anti-VACV IgG was determined by ELISA, and seven MPXV genomes were sequenced. A total of 3,095 cases were included, 816 (26%) with positive MPXV-PCR results. Most positive cases were men in their 30s and MSM. A total of 285 (35%) MPXV-PCR+ patients lived with HIV. Eight were coinfected with varicella-zoster virus. Anogenital lesions and adenomegaly were associated with the diagnosis of mpox. Females and individuals under 18 represented 9% and 5% of all confirmed cases, respectively, showing higher PCR cycle threshold values and fewer anogenital lesions than adult men. Anti-VACV IgG was detected in 29/46 (63%) patients. All analyzed sequences belonged to clade IIb. In RJ state, mpox presented a diverse clinical picture, represented mainly by mild cases with low complication rates and prominent genital involvement. The incidence in females and children was higher than usually reported. The observation of a bimodal distribution of Ct values, with few positive results, may suggest the need to review the diagnostic criteria in these groups.

Interferon-induced helicase C domain-containing protein 1 (IFIH1) is one of the main pattern recognition receptors that sense viral RNA and activate host cells to mount an effective antiviral immunity. Therefore, a case-control study (90 patients with mild/moderate COVID-19 and 90 matched controls) was performed to explore the association of two variants of the IFIH1 gene with COVID-19 risk using the tetra-primer amplification refractory mutation system-polymerase-chain-reaction method. The first is a missense variant, rs1990760 C/T, and the second is an intergenic variant, rs2111485 A/G. In addition, serum IFIH1 levels were assessed using an ELISA kit. Results revealed that mutant alleles ( T and G, respectively) and corresponding homozygous genotypes (TT and GG, respectively) of both variants were significantly associated with increased risk of COVID-19. IFIH1 levels were significantly higher in patients compared to controls and were favorably affected by the rs1990760 and rs2111485 mutant-type genotypes. In conclusion, IFIH1 protein showed up-regulated levels in the serum of patients with mild/moderate COVID-19. In addition, the IFIH1 gene variants rs1990760 C/T and rs2111485 A/G were associated with susceptibility to COVID-19, and the study suggests that their mutant-type genotypes are not only associated with increased risk of COVID-19 but also contributed to higher serum IFIH1 levels.

Obesity has been identified as an independent risk factor for severe outcomes in humans with coronavirus disease 2019 (COVID-19) and other infectious diseases. Here, we established a mouse model of COVID-19 using the murine betacoronavirus, mouse hepatitis virus 1 (MHV-1). C57BL/6 and C3H/HeJ mice exposed to MHV-1 developed mild and severe disease, respectively. Obese C57BL/6 mice developed clinical manifestations similar to those of lean controls. In contrast, all obese C3H/HeJ mice succumbed by 8 days post-infection, compared to a 50% mortality rate in lean controls. Notably, both lean and obese C3H/HeJ mice exposed to MHV-1 developed lung lesions consistent with severe human COVID-19, with marked evidence of diffuse alveolar damage (DAD). To identify early predictive biomarkers of worsened disease outcomes in obese C3H/HeJ mice, we sequenced RNA from whole blood 2 days post-infection and assessed changes in gene and pathway expression. Many pathways uniquely altered in obese C3H/HeJ mice post-infection aligned with those found in humans with severe COVID-19. Furthermore, we observed altered gene expression related to the unfolded protein response and lipid metabolism in infected obese mice compared to their lean counterparts, suggesting a role in the severity of disease outcomes. This study presents a novel model for studying COVID-19 and elucidating the mechanisms underlying severe disease outcomes in obese and other hosts.

Background: Major screening abnormalities in pre-colposcopic stage are tests results that imply direct referral to colposcopy (and/or expedited treatment) without performing additional high-grade squamous intraepithelial lesions or worse (HSIL+) risk selection testing. Currently, both clinically validated HSIL+ risk selection tests, reflex cytology and reflex p16/Ki67 dual staining (DS), are being compared for use in primary HPV-based screening to avoid possible overtreatment, but there is still no sufficient data available for their performance. Methods: Among 30,066 liquid-based cervical cancer screening tests results, a group of 332 women was selected with available HRHPV tests results with 16/18 limited genotyping, liquid-based cytology, DS, and histology results from standardized colposcopy with biopsy. In HPV 16/18+ cases, three triage approaches were retrospectively analyzed. Predictive values for detection of HSIL+ were calculated and number of colposcopies required in each strategy. Results: Both triage models with DS used (reflex cytology followed by DS, and reflex DS alone in all cases) had significantly higher PPV for HSIL+ than strategy with reflex cytology alone (44.2%/45.7% vs. 28.3%; p<0.0001). In models with DS, less colposcopies were required (95/92 vs. 152) and less colposcopies were needed per HSIL+ detection (2,26/2,19 vs. 3,54). Only 1 HSIL+ case was missed in both triage models with DS incorporation. Conclusions: p16/Ki67 dual-stain may be an effective, alone or combined with cytology, triage test to detect HSIL+ in patients with major screening abnormalities in primary HPV-based cervical cancer screening. Performing cytology as the first triage test improves the strategy by enabling referrals to expedited treatment in selected cases.

Influenza constitutes a critical respiratory infection that imposes significant public health burdens. The precise influence of these pollutants on influenza activity remains unclear. This study aimed to investigate the effects of different air pollutants on the incidence of influenza-like illness (ILI), influenza A (Flu A), and influenza B (Flu B) in China based on nationwide data on air pollution and the influenza data from 554 sentinel hospitals across 30 provinces and municipalities from 2014 to 2017. Distributed Lag Nonlinear Model (DLNM) was employed to discern the lagged effects amid the concentrations of six distinct air pollutants, namely PM2.5, PM10, O 3, CO, SO 2, and NO 2, and the incidence of ILI, Flu A, as well as Flu B. Our analysis indicated that there was generally no distinction in the effects of air pollutants on the incidence of ILI, Flu A, and Flu B, although variations existed in terms of the specific level of risk associated with each of these categories. Specifically, elevated levels of PM2.5, PM10, CO, SO 2, and NO 2 were predominantly associated with an increased risk of influenza. In contrast, the effect of O 3 concentration on influenza was bidirectional whereby it promoted influenza outbreaks at low and high levels.

The mid-term impact of SARS-CoV-2 infection on senescence profile and immune checkpoints biomarkers in people living with HIV (PLWH) was assessed. Cross-sectional study in 95 PLWH on ART stratified by SARS-CoV-2 infection: a) 48 PLWH previously infected (PCR+) (HIV/SARS); b) 47 PLWH controls without previous infection (HIV). Plasma biomarkers (n=44) related to cell immune checkpoint molecules, associated with the Senescence-Associated Secretory Phenotype (SASP), and related to pro and anti-inflammatory cytokines were assessed by Procartaplex Multiplex Immunoassays (Xmap-Luminex technology). Differences between groups were analyzed using a generalized linear model, adjusted by sex and ethnicity and corrected by false discovery rate. Significant values were defined as the adjusted arithmetic mean ratio ≥1.2 or ≤0.8; q-value<0.1. The relationship between plasma biomarkers was evaluated by Spearman correlation (significant correlations rho≥0.3 and q-value<0.1). PLWH had a median age of 45 years and 80% were men. All PLWH infected by SARS-CoV-2 had a symptomatic infection, 83.3% as mild, and with a median of 12 weeks after diagnosis of SARS-CoV-2 infection. HIV/SARS group showed higher levels of the cell immune checkpoint plasma biomarkers CD80, PDCD1LG2, CD276, PDCD1, CD47, HAVCR2, TIMD4, TNFRSF9, TNFRSF18, and TNFRSF14 respect to HIV group. The SASP biomarkers LTA, CXCL8, and IL13 and the inflammatory biomarkers IL4, IL12B, IL17A, CCL3, CCL4, and INF1A showed significantly higher levels in the HIV/SARS group. SARS-CoV-2 infection in PLWH leads to significant medium-term disruption in plasma immune checkpoint molecules and inflammatory cytokines, highlighting SASP-related. This could be a risk factor for the emergence of complications in PLWH.

Background: Starting from May 31 st, 2023, the local transmission of monkeypox (Mpox) in mainland China began in Beijing. Till now, the transmission characteristics have not been explored. Method: Based on the daily Mpox incidence data in the first three weeks of Beijing (from May 31 st to June 21 st, 2023) , we employed the instant-individual heterogeneity transmission model to simultaneously calculate the effective reproduction number ( R e) and the degree of heterogeneity ( k) of the Beijing epidemic. We additionally simulated the monthly infection size in Beijing from July to September and compared with the reported data to project subsequent transmission dynamics. Results: We estimated R e to be 1.68 [95% HPD:1.12, 2.41], and k to be 2.57 [95% HPD: 0.54, 83.88], suggesting the transmission of Mpox in Beijing was supercritical and didn’t have considerable transmission heterogeneity. We projected that R e fell in the range of 0.95 to 1.0 from July to September, highlighting more efforts needed to further reduce the Mpox transmissibility. Conclusion: Our findings revealed supercritical and homogeneous transmission of the Mpox epidemic in Beijing. Our results may provide reference for understanding and predicting of the on-going Mpox transmission in other regions of China and assess the effect of control measures.

Objective: This study investigated the efficacy of the prophylactic human papillomavirus (HPV) vaccine started at 2009- 2013 in Japan. Materials and Methods: The study involved 1529 eligible women aged 16 to 39 years who visited 11 outpatient clinics for various reasons in Japan. All these patients underwent an examination of HPV genotype and a Pap test using cervical cell samples. Two hundred ninty-nine women (19.6%) received the prophylactic HPV vaccine (bivalent :quadrivalent vaccine ratio = 2:1). Of the 5062 participants in the Japanese Human Papillomavirus Disease Education and Research Survey (J-HERS 2011), which was conducted in the pre-vaccination era, 3236 eligible participants were included as controls. Results: In the present study (J-HERS 2021), highest rate for HPV vaccination (53%) was observed in 22- to 27-year-old patients. Vaccinated ones showed 49% protection against low-grade intraepithelial lesions (LSIL) and atypical squamous cells not excluding high-grade squamous intraepithelial lesions (ASCH) or worse (LSIL/ASCH+), and 100% protection against high-grade squamous intraepithelial lesions (HSIL) or worse (HSIL+). The prevalences of HPV16 and HPV18 infections also significantly decreased (HPV16; 95% and HPV18; 100%), but there were no differences in HPV6 and HPV11 infections by the vaccination. The prevalences of HPV51 and HPV59 increased with vaccination, although these changes were not confirmed in the comparative study with J-HERS 2011. Comparisons between the pre-vaccination period (J-HERS 2011) and post-vaccination period (J-HERS 2021) revealed reduction rates of 43%, 51%, 88%, and 62% were observed for HPV16, HPV18, HPV16/18, and HPV31/58 infections, respectively. Similarly, reduction rates of 62% and 71% for LSIL/ASCH+ and HSIL+, respectively. The reduction rate for LSIL/ASCH+ was 88% in 16- to 21-year-old patients, whereas the rate for HSIL+ was 87% in 28- to 33-year-old patients. C onclusion: Bivalent or quadrivalent vaccines provided 100% protection against high-grade squamous cell lesions (suggestive of CIN2 or CIN3) in young women aged < 39 years at 9 to 12 years after initiation of the first nationwide HPV vaccination program in Japan. Cross-protection against HPV31 and HPV58 is likely to occur, although some HPV type replacements are inconsistent across vaccination regimens. This demonstrates a high effectiveness of HPV vaccine. In contrast, we worry about no reduction of cervical cancer in younger generation (born in 1997-2007) who are rarely vaccinated due to long term suspension of this vaccine recommendation in Japan.

The precise effects of infection and maternal vaccination during pregnancy on the fetus remain uncertain. Therefore, this study aims to investigate the immunological responses triggered by SARS-CoV-2 exposure or vaccination in pregnant women. However, we also evaluated the vertical antibody transmission and the persistence of immunity in infants up to six months post-birth. The study recruited pregnant women admitted for labor and delivery in Fortaleza, Brazil, between January 2021 and March 2022. Participants aged 18 or older with flu-like symptoms were included. Nasopharyngeal swabs and blood samples were collected for COVID-19 testing and antibody detection for the viral Nucleocapsid (N) and Spike (S) of SARS-CoV-2. Participants were categorized as Unvaccinated or Vaccinated, and further divided based on PCR test results. Blood or plasma samples were collected at birth and from infants at six months postpartum. We included 76 mother-infant dyads, 11 in the unvaccinated/PCR-/IgG+, 39 in the unvaccinated/PCR+, 20 in the vaccinated/PCR- and 6 in the vaccinated/PCR+. Analysis of maternal serological profiles showed no significant differences in anti-N IgG levels between unvaccinated and vaccinated groups. However, anti-S IgG titers were significantly higher in vaccinated mothers. The ratio of anti-S IgG antibody transfer from vaccinated mothers to infants was notably higher, especially in the Unvaccinated/PCR+ group compared to the Vaccinated/PCR- group. Furthermore, infants born to vaccinated mothers maintained seroconversion at six months, while those born to unvaccinated mothers did not. Maternal vaccination, particularly during the second trimester, results in a significantly higher transplacental transfer ratio. This leads to elevated anti-S IgG antibody levels in cord blood and infants at six months of age. The study emphasizes the importance of vaccination protocols in optimizing antibody transfer and persistence.

Olfactory dysfunction was one of the most common symptom of infection with the Wuhan strain of SARS-CoV-2 and could persist for several months after symptom onset. The pathogenesis of prolonged olfactory dysfunction (OD) remains poorly understood but probably involves sustained viral replication associated with limited mucosal immune response to the virus. This prospective study was conducted to investigate the potential relationship between nasal SARS-CoV-2 viral load and antibody levels in patients with loss of smell. One hundred and five patients were recruited 2 weeks after presenting with confirmed COVID-19 associated OD. Based on the identification sniffing test performed at enrollment, 52 patients were still anosmic or hyposmic and 53 were normosmic. SARS-CoV-2 was detectable in nasal wash of about 50% of anosmic and normosmic patients. Higher viral load was detected in anosmic patients with lower levels of SARS-CoV-2 specific nasal IgG and IgA. This association was not observed in normosmic patients. No relationship between nasal viral load and antibodies to endemic coronaviruses was observed. SARS-CoV-2 replication in the nasal cavity may be promoted by defective mucosal antibody responses in patients with OD. Boosting mucosal immunity may limit nasal SARS-CoV-2 replication and thereby help in the control of persistent OD.

Comment on Shao et al.’s “risk factors associated with COVID‐19 pneumonia in Chinese patients with pre‐existing interstitial lung disease during the SARS‐CoV‐2 pandemic”Hsiu-Ming Lee 1, Po-Cheng Shih 2,3, James Cheng-Chung Wei, MD, PhD 2,4,51 School of Medicine, China Medical University, Taichung, Taiwan2 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan3 Department of Allergy, Immunology & Rheumatology, Changhua Christian Hospital, Changhua, Taiwan4 Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan5 Graduate Institute of Integrated Medicine, China Medical University, Taichung, TaiwanHsiu-Ming Lee and Po-Cheng Shih contribute equally.Correspondence： James Cheng-Chung Wei, MD, PhD.Address : No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung City 40201, Taiwan.TEL : ＋886 4 24739595 #34718. (FAX) +886 4 24637389E-mail : [email protected] 0000-0002-1235-0679Word counts: 498Table counts: 0Figure counts: 0Funding Sources : noneConflicts of Interest : The authors declare no conflicts of interest.Dear Editor,We read the article with great interest by Shao et al, where a retrospective study analyzed the risk factors for pneumonia related to the 2019 coronavirus disease (COVID-19) in patients with various types of interstitial lung disease (ILD) caused by SARS-CoV-2 infection. According to Cox’s multivariate analysis, only male gender and the use of corticosteroids emerged as risk factors for developing new coronavirus pneumonia following illness. On the other hand, receiving two to three doses of vaccination proved protective for individuals with preexisting ILD who contracted COVID-19 pneumonia.[1] As a result, it is recommended that patients with preexisting ILD, especially those who are male and using corticosteroids, receive more than two doses of the vaccine for enhanced protection. Since 2019, WHO has reported 770 million confirmed COVID-19 cases and 6.9 million deaths globally.[2] Studies have linked interstitial lung disease to worse COVID-19 outcomes, showing a four-fold mortality increase.[3] Interstitial lung disease includes inflammatory and fibrotic conditions, with incidence rates of 7 to 1,650 per 100,000.[4, 5] In contrast, COVID-19 can also trigger interstitial lung disease.[6] As COVID-19 spreads, global lung disease rates will increase. Identifying risk factors for interstitial lung disease after a COVID-19 diagnosis is crucial for early prevention, resource allocation, and effective management. However, some details in the article still need to be further clarified.First, this paper analyzed several variables in developing pneumonia during COVID-19 infection, including age, sex, vaccination history, common immunosuppressants, antifibrotic agents, and corticosteroids. However, it should be noted that certain risk factors, such as smoking, diabetes mellitus, autoimmune diseases, and recurrent COVID-19 infections, still exhibit a high association with pneumonia and were not included in the analysis.[7-9] Therefore, we recommend that the authors consider incorporating these factors into future similar studies. The paper analyzed corticosteroid use as a potential risk factor but without mentioning the timing of administration. The Centers for Disease Control and Prevention (CDC) recommends steroids for COVID-19 cases beyond a sure severity threshold. Failing to differentiate when they were given may overestimate the proportion of pneumonia cases using steroids, affecting p-values. Some ILD patients use multiple immunosuppressants, impacting immune function and COVID-19 pneumonia risk. While the article lists common medications, it doesn’t analyze the number of patients receiving combined therapy. Therefore, we recommend that future studies assess the risk associated with concurrently using immunosuppressants to understand the implications of combination therapy better.Second, this paper reveals an intriguing shift, as sarcoidosis appears to become a protective factor against pneumonia following a COVID-19 diagnosis. It could be a groundbreaking revelation since the articles consistently state that sarcoidosis is an excessively high-risk factor for severe COVID-19 pneumonia.[10] No literature has delved into this phenomenon, its mechanisms, or potential implications. Given the substantial representation of sarcoidosis patients in this study, we recommended that authors separately analyze its subgroup, examining their disease site, activity, severity, and medication use differences. Furthermore, future research should focus on investigating the interaction mechanisms and conducting comprehensive comparative studies to unlock the full potential of this discovery.References:1. Shao, C., et al., Risk factors associated with COVID-19 pneumonia in Chinese patients with pre-existing interstitial lung disease during the SARS-CoV-2 pandemic. J Med Virol, 2023.95 (9): p. e29098.2. WHO Coronavirus (COVID-19) Dashboard . 2023 [cited 2023 Oct 10, 2023]; Available from:https://covid19.who.int/.3. Valenzuela, C., G. Waterer, and G. Raghu, Interstitial lung disease before and after COVID-19: a double threat? Eur Respir J, 2021.58 (6).4. Shah Gupta, R., et al., Incidence and prevalence of interstitial lung diseases worldwide: a systematic literature review.BMJ Open Respir Res, 2023. 10 (1).5. Lee, C.Y., Interstitial lung disease-From pulmonary perspective to pathogenesis, multidisciplinary approach and treatment. Int J Rheum Dis, 2023. 26 (5): p. 823-824.6. Myall, K.J., et al., Persistent Post-COVID-19 Interstitial Lung Disease. An Observational Study of Corticosteroid Treatment. Ann Am Thorac Soc, 2021. 18 (5): p. 799-806.7. Strzelak, A., et al., Tobacco Smoke Induces and Alters Immune Responses in the Lung Triggering Inflammation, Allergy, Asthma and Other Lung Diseases: A Mechanistic Review. Int J Environ Res Public Health, 2018. 15 (5).8. Wang, W., et al., Clinical characteristics of moderate or severe COVID-19 infection in patients with rheumatic diseases and analysis of risk factors leading to severe disease. Int J Rheum Dis, 2023. 26 (10): p. 1951-1959.9. Batu, E.D. and A. Erden, The outcome of COVID-19 in patients with autoimmune rheumatic diseases: Comparable to the general population or worse? Int J Rheum Dis, 2023. 26 (8): p. 1435-1439.10. Tana, C., et al., Sarcoidosis and COVID-19: At the Cross-Road between Immunopathology and Clinical Manifestation. Biomedicines, 2022.10 (10).

Introduction: In our study, we aimed to evaluate the effect of high dose intravenous anakinra treatment on development of thrombotic events in severe and critical COVID-19 patients. Material and methods: This retrospective observational study was conducted at a tertiary referral center in Aksaray, Turkey. The study population consisted of two groups as follows; the patients receiving high dose intravenous anakinra (anakinra group) added to background therapy and the patients treated with standard of care (SoC) as historical control group. Age, gender, mcHIS scores, and comorbidities such as DM, HT, and CHD of the patients were determined as the variables to be matched. Results: We included 114 patients in SoC and 139 patients in Anakinra group into the study. Development of any thromboembolic event (5% vs 12.3%, p=0.038; OR:4.3) and PTE (2.9% vs 9.6%, p=0.023; OR:5.1) were lower in Anakinra group than SoC. No patient experienced CVA and/or clinically evident DVT both in two arms. After 1:1 PS matching, 88 patients in SoC and 88 patients in Anakinra group were matched and included into the analysis. In survival analysis, development of any thromboembolic event, PTE, and MI were higher in SoC compared to Anakinra. Survival rate was also lower in patients with SoC arm than Anakinra in patients who had any thromboembolic event as well as MI. Conclusion: In our study, development of thrombosis were associated with hyperinflammation in patients with severe and critical COVID-19. Intravenous high-dose anakinra treatment decreases both venous and arterial events in patients with COVID-19.

Introduction : In intensive care units, COVID-19 viral pneumonia patients (VPP) present symptoms similar to those of other patients with non-viral infection (NV-ICU). To better manage VPP, it is therefore interesting to better understand the molecular pathophysiology of viral pneumonia and to search for biomarkers that may clarify the diagnosis. The secretome being a set of proteins secreted by cells in response to stimuli represents an opportunity to discover new biomarkers. Aims : Identify secretomic signatures of VPP with those NV-ICU. Methods : Plasma samples and clinical data from NV-ICU (n=104), VPP (n=30) or healthy donors (HD, n=20) were collected at Nantes Hospital (France) upon admission. Samples were enriched for the low-abundant proteins and analyzed using non-target mass spectrometry. Specifically deregulated proteins (DEP) in VPP versus NV-ICU were selected. Combinations of 2 to 4 DEPs were established. Results : The differences in secretome profiles of the VPP and NV-ICU groups were highlighted. Forty-one DEPs were specifically identified in VPP compared to NV-ICU. Five combinations of 3 proteins with a receiver operating characteristic curve presenting an area under the curve of 95.0% were identified. Conclusion: This study identifies five combinations of candidate biomarkers in VPP compared to NV-ICU that may help distinguish the underlying causal molecular alterations.

Title: COVID-19 and Autoimmunity: Do We Need More Evidence?