Severe fever with thrombocytopaenia syndrome virus (SFTSV) and Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause the hyperproduction of inflammatory cytokines, which have pathological effects in patient including severe or fatal cytokine storms. To characterize the effect of SFTSV and SARS-CoV-2 infection on the production of cytokines in SFTS and COVID-19 patients, we performed an analysis of cytokines in SFTS and COVID-19 patients and also investigated the role of IL-10 in vitro studies: LPS-induced THP-1-derived macrophages, SFTSV infection of THP-1 cells, and SARS-CoV-2 infection of THP-1 cells. In this study, we found that levels of both IL-10 and IL-6 were significantly elevated, the level of TGF-β was significantly decreased and IL-10 was elevated earlier than IL-6 in severe and critical COVID-19 and fatal SFTS patients, and inhibition of IL-10 signalling decreased the production of IL-6 and elevated that of TGF-β. Therefore, the hyperproduction of IL-10 and IL-6 and the low production of TGF-β have been linked to cytokine storm-induced mortality in fatal SFTS and severe and critically ill COVID-19 patients and that IL-10 can play an important role in the host immune response to severe and critical SARS-CoV-2 and fatal SFTSV infection.

In somatic cells, microRNAs (miRNAs) bind to the genomes of RNA viruses and influence their translation and replication. Here we demonstrate that a significant number of miRNA binding sites locate in the NSP4 region of the SARS-CoV-2 genome, and the intestinal human miRNAs exert evolutionary pressure on this region. Notably, in infected cells, NSP4 promotes the formation of double-membrane vesicles, which serve as the scaffolds for replication-transcriptional complexes and protect viral RNA from intracellular destruction. In three years of selection, the loss of many miRNA binding sites, in particular, those within the NSP4, has shaped the SARS-CoV-2 genomes to promote the descendants of the BA.2 variants as the dominant strains that define current momentum of the pandemics. Findings highlight the possibility that intestinal tissue may significantly impact evolution of the SARS-CoV-2 genome and may play a pivotal role in the long COVID.

COVID-19 infection and Leser-Trelat sign: is there an association?Farhad Handjaniab, Roya Radanfarab, Mozhdeh Sepaskhahab*, Niloofar Dehdari EbrahimicaMolecular Dermatology Research Center, Shiraz University of Medical Sciences, Shiraz, IranbDepartment of Dermatology, Shiraz University of Medical Sciences, Shiraz, IrancStudent Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran*corresponding author

Background We estimated the secondary attack rate of SARS-CoV-2 among household contacts of PCR-confirmed cases of COVID-19 in rural Kenya and analysed risk factors for transmission. Methods We enrolled incident PCR-confirmed cases and their household members. At baseline, a questionnaire, a blood sample, and naso-oropharyngeal swabs were collected. Household members were followed 4, 7, 10, 14, 21 and 28 days after the date of the first PCR-positive in the household; naso-oropharyngeal swabs were collected at each visit and used to define secondary cases. Blood samples were collected every 1-2 weeks. Symptoms were collected in a daily symptom diary. We used binomial regression to estimate secondary attack rates and survival analysis to analyze risk factors for transmission. Results A total of 119 households with at least one positive household member were enrolled between October 2020 and September 2022, comprising 503 household members; 226 remained in follow up at day-14 (45%). A total of 43 secondary cases arose within 14 days of identification of the primary case, 81 household members remained negative. The 7-day secondary attack rate was 4% (95%CI 1-10%), the 14-day secondary attack rate was 28% (95%CI 17-40%). Of 38 secondary cases with data, 8 reported symptoms (21%, 95%CI 8-34%). Antibody to SARS-CoV-2 spike protein at enrolment was not associated with risk of becoming a secondary case. Conclusion Households in our setting experienced a lower 7-day attack rate than a recent meta-analysis indicated as the global average (23-43% depending on variant), and infection is mostly asymptomatic in our setting.

Background: Priming with ChAdOx1 followed by heterologous boosting have been considered in several countries. Nevertheless, analyses that provide a comparison of the immunogenicity of heterologous booster in comparison to homologous primary vaccination regimens and natural infection are lacking. In this study, we aimed to conduct a comparative assessment of the immunogenicity between heterologous prime-boost vaccination using BNT162b2 or mRNA-1273 and homologous primary vaccination regimens. Methods: We matched vaccinated naïve individuals (VN; n=673) who had received partial vaccination (n=64), primary vaccination (n=590), or primary series plus one mRNA vaccine heterologous booster (n=19) with individuals with a documented primary SARS-CoV-2 infection and no vaccination record (natural infection; NI cohort; n=206). We measured the levels of neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA titers. Results: Homologous primary vaccination with ChAdOx1 not only showed less potent NTAb, TAb, anti-S-RBD IgG, and anti-S1 IgA immune responses compared to primary-BNT162b2 or mRNA-1273 vaccination regimens (P<0.05), but also showed ~3 fold less anti-S1 IgA response compared to infection-induced immunity (P<0.001). Nevertheless, heterologous booster dose resulted in a significant boost of at least ~12 folds in the immune response. Furthermore, correlation analyses revealed that both, anti-S-RBD IgG and anti-S1 IgA significantly contributed to virus neutralization among NI individuals, particularly in symptomatic and pauci-symptomatic individuals, whereas, among VN individuals, anti-S-RBD IgG was the main contributor to virus neutralization (r > 0.90, P < 0.001). Conclusion: The results emphasize the potential benefit of using heterologous mRNA boosters to increase antibody levels and neutralizing capacity.

Despite recent advances in prophylactic vaccination, SARS-CoV-2 infections continue to cause significant morbidity. A better understanding of immune response differences between vaccinated individuals with and without later SARS-CoV-2 breakthrough infection is urgently needed. CoV-ADAPT is a prospective long-term study comparing humoral (anti-spike-RBD-IgG, neutralization capacity, avidity) and cellular (spike-induced T-cell interferon-γ release) immune responses in individuals vaccinated against SARS-CoV-2 at four different time points (three before and one after third vaccination). In this cohort study, 62 fully vaccinated individuals presented with SARS‑CoV-2 breakthrough infections vs 151 without infection 3-7 months following third vaccination. Breakthrough infections significantly increased anti-spike-RBD-IgG (p<0.01), but not spike-directed T-cell interferon-γ release (TC), antibody neutralization capacity or avidity. Anti-spike-RBD-IgG and antibody avidity decreased with age (p<0.01) and females showed higher anti-spike-RBD-IgG (p<0.01), and a tendency towards higher antibody avidity (p=0.051). The association between humoral and cellular immune responses previously reported at various time points was lost in subjects after breakthrough infections (p=0.807). Finally, a machine-learning approach based on our large immunological data set (a total of 49 variables) from different time points was unable to predict breakthrough infections (AUC: 0.55). In conclusion, distinct differences in humoral vs cellular immune responses in fully vaccinated individuals with or without breakthrough infection could be demonstrated. Breakthrough infections predominantly drive the humoral response without boosting the cellular component. Breakthrough infections could not be predicted based on immunological data, which indicates a superior role of environmental factors (e.g. virus exposure) in individualized risk assessment.

Background First Few “X” (FFX) studies provide evidence to guide public health decision making and resource allocation. The adapted WHO Unity FFX protocol for COVID-19 was implemented to gain an understanding of the clinical, epidemiological, virological, and household transmission dynamics of the first cases of COVID-19 infection detected in Juba, South Sudan. Methods Laboratory-confirmed COVID-19 cases were identified through the national surveillance system, and an initial visit was conducted with eligible cases to identify all close contacts. Consenting cases and close contacts were enrolled between June 2020 and December 2020. Demographic, clinical information and biological samples were taken at enrolment and 14–21 days post-enrolment for all participants. Results Twenty-nine primary cases and 82 contacts were included in analyses. Most primary cases (n=23/29, 79.3%) and contacts (n=61/82, 74.4%) were male. Many primary cases (n=18/29, 62.1%) and contacts (n=51/82, 62.2%) were seropositive for SARS-CoV-2 at baseline. The secondary attack rate among susceptible contacts was 12.9% (4/31; 95% CI: 4.9%–29.7%). All secondary cases and most (72%) primary cases were asymptomatic. Reported symptoms included coughing (n=6/29, 20.7%), fever or history of fever (n=4/29, 13.8%), headache (n=3/29, 10.3%) and shortness of breath (n=3/29, 10.3%). Of 38 cases, two were hospitalised (5.3%) and one died (2.6%). Conclusions These findings were used to develop the South Sudanese Ministry of Health surveillance and contract tracing protocols, informing local COVID-19 case definitions, follow-up protocols and data management systems. This investigation demonstrates that rapid FFX implementation is critical in understanding the emerging disease and informing response priorities.

Objective: A qualitative study sought to understand the transition experiences of United States (U.S.) military Service members found “unfit for duty” following medical and physical evaluation boards (MEBs and PEBs). Methods: Confidential telephone interviews were conducted with 25 current and prior Service members. Participants were asked to share their experiences before, during, and after the MEB and PEB processes. To that end, interview questions were designed to gather the following types of transition experiences: (1) health conditions experienced during the medical disability evaluation process; (2) reactions to being recommended for separation, (3) transition-related stress and challenges, and (4) coping strategies. Salient themes were identified across chronological narratives. Results: Conditions that participants’ experienced included debilitating physical (e.g., injury) and/or mental health (e.g., post-traumatic stress disorder) conditions. In response to the “unfit for duty” notice, some participants reported emotional distress (e.g., anxiety, sadness, anger) connected to a sense of uncertainty about the future. Other participants reported relief connected to a sense of progression toward their medical disability claim status. Transition stress included the length of the MEB/PEB process, impact of the COVID-19 pandemic on the process, experiences of financial stress, impact on family life, and the compounded effect of these stressors on emotional distress, including depression and suicidal thoughts. Participants reported using adaptive (e.g., psychotherapy) and maladaptive (e.g., excessive drinking) strategies to cope with stress. Conclusions: The notable emotional distress and transition stress experienced by Service members found “unfit for duty” highlight the need for increased support and interventions to facilitate adaptive coping strategies during this vulnerable period.

Background: As the ongoing public health crisis from Coronavirus Disease 2019 (COVID-19) pandemic puts strains on current models of cancer care, many health care centers had to adapt to minimize the risk of exposure and infection. The effects of the COVID-19 pandemic in a comprehensive cancer center were determined. Purpose: To measure the impact of the COVID-19 pandemic on care delivery at a comprehensive cancer center. Methods: The number of on-site and telehealth visits (TH) were obtained from scheduling software. Multiple factors including total visits, telehealth visits, screenings for cancer diagnosis, and cancer treatments were tracked from two years before the pandemic onset through 2022. The length of stay (LOS) and Case Mix Index (CMI) were calculated using hospital database. Results: In the third quarter of FY 2020, telehealth visits (TH) represented a fifth of total patient encounters. Cancer treatments, such as chemotherapy, radiation therapy, and surgery, decreased during the pandemic with number of surgeries being most affected (23% decrease in 2020 compared to the previous fiscal year). The average length of stay (LOS) was also longer with less discharges per given time during the pandemic. The increased LOS was related to increased severity of patient illnesses since CMI was higher. Screening mammograms decreased to a nadir of 58% in 2021 as compared to those screened in pre-pandemic fiscal years. Conclusions : The COVID-19 pandemic impacted many aspects of care, such as treatment and screenings. Many of these factors had to be postponed due to the fear of acquiring COVID-19 and access to care. The findings presented implicate that the delays and changes in cancer care during the pandemic resulted in less screening and treatment of more advanced disease.

Introduction: In this paper we examine the relationship between vaccination against COVID-19 and both the death rate from COVID-19 and the rate of COVID-19 spread. Our goal is determine if vaccination is associated with reduced death and/or spread of disease at the local level. Methods: This analysis was conducted at the county level in the state of Pennsylvania, United States of America, with data that were collected during the first half of 2022 from the state of Pennsylvania’s Covid Dashboard ([COVID-19 Data for Pennsylvania (pa.gov)](https://www.health.pa.gov/topics/disease/coronavirus/pages/cases.aspx) . Result s: Given that, during this time period, the vaccines being used were not geared specifically toward the common variants at that time, we found no statistically significant relationship between disease spread and vaccination rate at the county level. That said, we did find a highly statistically significant relationship between death rate and vaccination rate (p-value = 0.006). Specifically, a 1% increase in vaccination rate was found to correspond to a 0.751% decrease in death rate (95% confidence interval (0.236%, 1.266%)). Conclusions: These results support previous findings from across the world that Covid vaccination is highly efficacious in preventing death from the disease. Even during a time when vaccine design was not optimally matched with the prevailing strains, vaccination was found to reduce death rate. Hence, improving global vaccine availability is vitally important, in order to achieve necessary outcomes.

Objectives In a COVID-19 sero-surveillance cohort study with predominantly healthy and vaccinated individuals, the objectives were (i) to investigate longitudinally the factors associated with the quantitative dynamics of anti-spike IgG antibody levels, (ii) to evaluate whether the antibody levels were associated with protection from SARS-CoV-2 infection and (iii) to assess whether the association was different in the pre-Omicron compared with the Omicron period. Methods The QuantiVac Euroimmun ELISA test was used to quantify anti-S1 IgG levels. The entire study period (16 months), the 11-month pre-Omicron period and the cross-sectional analysis prior to the Omicron surge included 3219, 2310 and 895 reactive serum samples from 949, 919 and 895 study participants, respectively. Mixed-effect linear, mixed-effect time-to-event and logistic regression models were used to achieve the objectives. Results Age and time since infection or vaccination were the only factors associated with a decline of anti-S1 IgG levels. Antibody levels were significantly associated with protection from SARS-CoV-2 infection, and the association was higher for the Omicron than for the Alpha and Delta variants. In a prediction model, it was estimated that >8000 BAU/mL anti-S1 IgG was required to reduce the risk of infection with Omicron variants by 20% to 30% for 90 days. Conclusions Anti-S1 IgG antibody levels are associated with protection from infection. The levels in the pre-Omicron periods were less significant than during the Omicron surge, which in turn required very high levels for protection in a statistical model.

Objectives: Circulating nucleocapsid (NCP) antigen of SARS-CoV-2 is increased in severely ill COVID-19 patients. However, clinical deterioration of COVID-19 often happens about one week after benign initial presentation. The role of NCP antigenemia as a biomarker in those cases remains unclear. We investigated NCP clearance kinetics in hospitalized patients as a risk assessment tool for predicting necessity of intensive care treatment of COVID-19 patients. Methods: Serum NCP was quantified using a commercial NCP-specific ELISA in hospitalized COVID-19 patients (n=63) during their hospital stay. Results were correlated to COVID-19 disease severity, inflammation parameters, antibody response and results of SARS-CoV-2 PCR from nasopharyngeal swabs.   Results: We demonstrate that NCP antigen levels in serum remained elevated in 45.6% of patients requiring treatment on intensive care units (ICU) after >8 days post positive SARS-CoV-2 PCR, compared to complete clearance in all non-ICU patients. This was in contrast to mucosal clearance of virus as measured by PCR. Antigen clearance was associated with higher IgG against S1 but not NCP.   Conclusions: Detection of NCP antigenemia after 8 days post COVID-19 diagnosis identifies patients who will require intensive care. Lack of NCP clearance after one week can thus help to assess the risk to develop severe COVID-19.

Background: People with cystic fibrosis (PwCF) have chronic lung disease and may be at increased risk of COVID-19-related morbidity and mortality. This study aimed to determine seroprevalence and clinical characteristics of SARS-CoV-2 infection in children with CF, and to assess antibody responses following SARS-CoV-2 infection or vaccination. Methods: Children and adolescents with CF followed at Seattle Children’s Hospital were enrolled between July 20, 2020 and February 28, 2021. SARS-CoV-2 serostatus was determined on enrollment, at 6 and 11 months (+/-2 months) for nucleocapsid and spike IgG. Participants completed intake and weekly surveys inquiring about SARS-CoV-2 exposures, viral/respiratory illnesses, and symptoms. Results: Of 125 PwCF enrolled, 14 (11%) had positive SARS-CoV-2 antibodies consistent with recent or past infection. Seropositive participants were more likely to identify as Hispanic (29% vs 8%, p=0.04) and have pulmonary exacerbations requiring oral antibiotics in the year prior (71% vs 41%, p = 0.04). Five seropositive individuals (35.7%) were asymptomatic, while six (42.9%) reported mild symptoms, primarily cough and nasal congestion. Anti-spike protein IgG levels were approximately 10-fold higher in participants following vaccination compared with participants who had natural infection alone (p < 0.0001) and resembled levels previously reported in the general population. Conclusions: A majority of PwCF have mild or no symptoms of SARS-CoV-2 making it difficult to distinguish from baseline respiratory symptoms. Hispanic PwCF may be disproportionately impacted, consistent with racial and ethnic COVID-19 disparities among the general US population. Vaccination in PwCF generated antibody responses similar to those previously reported in the general population.

Widespread school closures and other non-pharmaceutical interventions (NPIs), used to limit the spread of SARS-CoV-2, significantly disrupted transmission patterns of seasonal respiratory viruses. As NPIs were relaxed, populations were vulnerable to resurgence. This study within a small community assessed acute respiratory illness among kindergarten through grade 12 students as they returned to public schools from September through December 2022 without masking and distancing requirements. The 277 specimens collected demonstrated a shift from rhinovirus to influenza. With continued circulation of SARS-CoV-2 and return of seasonal respiratory viruses, understanding evolving transmission patterns will play an important role in reducing disease burden.

Title pageTitle: Rust-colored patches of the lower extremity in a COVID-19 patientAuthrors: Jacem Rouatbi1, Mouna Korbi1*, Nouha Ben Abdeljalil2, Hichem Belhadjali1*, Jameleddine Zili1*

Abstract Introduction Telehealth and remote monitoring of patients of patients with mild COVID-19 infection have developed rapidly in response to the pandemic. Many healthcare systems have embraced telehealth for remote clinical monitoring and pulse oximetry for enhanced monitoring. Methods The experience of a large healthcare centre’s COVID Virtual Ward was reviewed retrospectively with a particular focus on evaluating the effectiveness, safety and utility of finger pulse oximetry within the home. Data from a 2 month period in early 2022 during a BA1 Omicron wave was retrospectively reviewed. 551 high risk patients were issued with pulse oximeters for monitoring oxygen saturations within their home. All patients received daily clinical review via telephone by a nurse or doctor. The group was highly vaccinated with only 6.4% of the cohort unvaccinated. Oximeters were promptly delivered via a courier service across a vast geographical area. Results Pulse oximetry was well utilised by most patients. Only 2.7% of the cohort demonstrated resting oxygen saturations of <94% during their Virtual Ward admission. Most patients reporting dyspnoea were able to be safely managed without escalation to an emergency department due to reassuring clinical and oximetry assessment. Home oxygen saturations correlated well with saturations recorded within the ED, with no patients found to have lower saturations compared with home saturations. Discussion Within a high risk population experiencing COVID-19 infection, pulse oximetry was a useful tool in clinical assessment and allowed a substantial reduction in COVID-19 related ED presentations.

New-onset pemphigus after COVID-19Yihang Xie1 Mei Yang1 Peimei Zhou1* Jiaming Fan1 Sijie Zhou11.Department of Dermatovenereology, Chengdu Second People’s Hospital, Chengdu, China* Corresponding Author: 46551704@qq.comrunning head: pemphigus after COVID‐19The category of the article: LetterKeywords: COVID‐19, pemphigusManuscript word count: 690 wordsThe number of figures: 2The number of tables: 0The number of references: 8Correspondence to: Peimei Zhou, M.D, Ph.D., Department of Dermatovenereology, Chengdu Second People’s Hospital, Qingyun Street, Chengdu, 610041, China.Tel: +86 18908176315; E-mail:46551704@qq.comFull conflict of interest statement: Y. Xie, and my co-authors have no conflict of interest to declare.Ethics statement: The patient has consented to publish this information.Data availability statement: Data sharing does not apply to this article as no new data were created or analyzed in this study.Funding sources: noneDear Editor,Cutaneous manifestations of coronavirus disease (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; family Coronaviridae, genus Betacoronavirus, subgenusSarbecovirus ), have been increasingly reported. SARS-CoV-2 infection is multisystemic and leads to potentially detrimental effects on various organs. Maculopapular, urticarial, vesicular, livedoid, and Chilblain-like lesions (CBLL) have been commonly reported to be associated with COVID-191. Here, we encountered an intriguing case of pemphigus that developed after COVID-19 infection.A 73-year-old male presented with a 42-day history of pruritic flaccid blisters that arose on the trunk and both upper limbs on normal and erythematous skin. Cutaneous lesions started 3 days after the positive reverse transcription polymerase chain reaction (RT-PCR) test diagnostic for SARS-CoV-2. He denied any history of systemic diseases, medication, and medicine or food allergies, and had not used any medication before symptom onset. The patient had first been diagnosed with allergic dermatitis caused by COVID-19 at another hospital and was prescribed oral prednisone (8 mg once daily for 4 days). The patient reported no new blisters, but the erythema did not fade; therefore, he visited our hospital. Physical examination revealed cutaneous lesions on the trunk and both upper limbs without mucosal involvement and scattered superficial blisters that developed into crusted erosions on an erythematous base(Figure1 A-D). Laboratory examination revealed normal white cell count (8.63 Ö109/L; normal 3.5-9.5 Ö109/L) with eosinophilia (6%; normal 0.5%-5.0%). Desmoglein (Dsg) 1 antibody levels were > 150 U/mL (positive: > 20), while Dsg3, BP(bullous pemphigoid)180, and BP230 antibody levels were within normal ranges. Other laboratory tests including RT-PCR targeting SARS-CoV-2, immunoglobulin, erythrocyte sedimentation rate, the spectrum of antinuclear antibodies, and T-spot were negative or normal. Chest and abdominal computed tomography revealed chronic inflammatory changes but no obvious tumors. Histological analysis of an incisional cutaneous biopsy taken from the patient’s abdomen showed subcorneal blister formation, acantholytic cells within the blister, and marked spongiotic edema in the spongiosa layer that had mixed inflammatory infiltrate with eosinophils, leukomonocytes, and neutrophils(Figure2A). Direct immunofluorescence (DIF) showed deposition of intracellular IgG and C3 in subepidermal 2/3 interspinous cells, though was negative for IgA and IgM, confirming pemphigus(Figure2B,C). Considering the good response to hormone treatment, the patient continued oral prednisone at 8 mg once daily along with the use of topical corticosteroids. Symptoms were completely absent after 3 weeks(Figure1 E-F).An increasing number of studies on cutaneous manifestations of COVID-19 have been reported; however, knowledge is still lacking on the common skin manifestations of this disease. Nonspecific cutaneous manifestations due to SARS-CoV-2 infection have also been reported, such as immune thrombocytopenic purpura (ITP), dengue-like exanthem, pityriasis rosea-like eruptions, acral ischemia, mucositis, dusky lesions, and bullae2.3.4. We searched all relevant articles and found only two cases of pemphigus vulgaris induced by COVID-19. In the case presented here, we realized that COVID-19 may be responsible for the rash eruption, possibly due to an inflammatory reaction5. The onset time of the rash was similar to that in the cases of pemphigus previously reported by De Medeiros5 and Mohaghegh F6 (within 1.5 months). In our case, although direct immunofluorescence showed subepidermal 2/3 deposition, we still diagnosed pemphigus foliaceus in combination with the pathological presentation, indirect immunofluorescence, and good treatment outcome. We speculate that the reason why direct immunofluorescence showed subepidermal 2/3 deposition may be the marked sponge edema of the epidermis, which may lead to a discontinuity of acantholysis, resulting in leakage of Dsg1 into the deeper epidermis.Pemphigus is defined as a group of rare mucocutaneous autoimmune diseases. Its etiology is unknown, though there are studies on autoimmune etiology which is believed to be related to stimulation by certain drugs, ultraviolet radiation, and malignant tumors; these induce autoimmune reactions by making the adhesive substances between the spiny cell layers become autoantigens7. It is rarely considered, however, that viral infections might cause pemphigus. The ability of SARS-CoV-2 to induce a hyper-stimulated immune state was discovered at the beginning of the pandemic8. As an instrumental trigger of autoimmunity, SARS-CoV-2 infection could be a trigger for autoimmune reactions, possibly through more than one mechanism. Because of this, all factors should be considered in any patient presenting with new-onset or exacerbating cutaneous reactions.

Over three years, humans have experienced multiple rounds of global transmission of SARS-CoV-2 and its variants. In addition, the widely used vaccines against SARS-CoV-2 involve multiple strategies of development and inoculation. Thus, the acquired immunity established among humans is complicated, and there is a lack of understanding within a panoramic vision. Here, we provide the special characteristics of the cellular and humoral responses in 2-year convalescents after inactivated vaccines, in parallel to vaccinated COVID-19 naïve persons and unvaccinated controls. The decreasing trends of the IgG, IgA, and NAb, but not IgM of the convalescents were reversed by the vaccination. Both cellular and humoral immunity in convalescents after vaccination were higher than the vaccinated COVID-19 naïve persons. Notably, inoculation with inactivated vaccine fueled the NAb to BA.1, BA.2, BA.4, and BA.5 in 2-year convalescents, much higher than the NAb during 6 months and 1 year after symptoms onset. And no obvious T cell escaping to the S protein was observed in 2-year convalescents after inoculation. The study provides insight into the complicated features of human acquired immunity to SARS-CoV-2 and variants in the real world, indicating that promoting vaccine inoculation is essential for achieving herd immunity against emerging variants, especially in convalescents.

We examined associations between mild or asymptomatic prenatal SARS-CoV-2 infection and preterm live birth in a prospective cohort study. During August 2020–October 2021, pregnant persons were followed with systematic surveillance for RT-PCR or serologically-confirmed SARS-CoV-2 infection until pregnancy end. The association between prenatal SARS-CoV-2 infection and preterm birth was assessed using Cox proportional-hazards regression. Among 954 pregnant persons with a live birth, 185 (19%) had prenatal SARS-CoV-2 infection and 123 (13%) had preterm birth. The adjusted hazard ratio for the association between SARS-CoV-2 infection and preterm birth was 1.28 (95% confidence interval 0.82-1.99, p=0.28), although results did not reach statistical significance.

Several biomarkers have been evaluated as predictors of severity or in directing the treatment of COVID-19, however there are no conclusive results with prediction of the pathobiology of the infection. In this study, we evaluated serum levels of cytokines, chemokines, and cell growth factors in association with the pathobiology of mild to moderate SARS-CoV-2 infection. Those markers may act as immuno-inflammatory biomarkers in adults with mild to moderate flu syndrome who sought care at health units. Serum levels of SARS-CoV-2 infected patients (n=113) and flu symptoms individuals negative for SARS-CoV-2 (n=58), tested by the RT-qPCR test - nasal swab were compared to healthy controls (n=53). Participants who were symptomatic but negative for SARS-CoV-2 were tested for Influenza A/B and Respiratory Syncytial Virus (RSV). Results showed that the pro-inflammatory cytokines IL-1β, MCP-3, TNF-α and G-CSF were increased in symptomatic patients and the cytokines IL-6 and IL-10 were associated with patients positive for SARS-CoV-2 when compared to healthy controls. Symptoms associated with COVID-19 were fever, anosmia, ageusia and myalgia. For patients without SARS-CoV-2 infection their major symptom was sore throat. Five percent (4/83) of SARS-CoV-2 negative patients were positive for RSV. The pathobiology of mild to moderate SARS-CoV-2 infection was associated with increasing pro-inflammatory cytokines and also a pleiotropic IL-6 and anti-inflammatory IL-10 cytokines compared to healthy controls.

The emergence of SARS-CoV-2 Omicron variant has led to a complete reconfiguration of the therapeutic landscape, with most monoclonal antibodies having lost any neutralization activity. We report here a case series of 75 immunocompromised patients infected by the Omicron variant who benefited of convalescent plasma. At baseline, 49 (68%) of the participants had a WHO score of 5 and 23 (32%) a WHO score of 6. At day 28 the case fatality was 24%. We observed no significant difference in the clinical outcome between patients with hematological malignancies, solid organ transplantation or auto-immune diseases. These promising results require controlled studies.

Changes in Conception Rates, Not in Pregnancy-Related Behavior, Likely Caused Decline in Pre-Term Births in Developed Countries During the First Year of the COVID-19 Pandemic 11* Corresponding author: Peter Fallesen, peter.fallesen@sofi.su.se, Swedish Institute for Social Research, Stockholm University, Stockholm 106 91, Sweden.Peter Fallesen, PhDSwedish Institute for Social Research, Stockholm University, Stockholm 106 91, Sweden ROCKWOOL Foundation, Ny Kongensgade 6, 1472 Copenhagen C, DenmarkMoritz Oberndorfer, DSc  Institute of Social Medicine, Center for Public Health, Medical University of Vienna, Kinderspitalgasse 15/1. Stock, A-1090, Vienna, Austria; MRC/CSO Social and Public Health Sciences Unit, University of Glasgow, Berkeley Square, 99 Berkeley Street, Glasgow, G3 7HR, UK  Population Research Unit, University of Helsinki, Unioninkatu 35 (P.O. Box 18). 00014 University of Helsinki, Finland  

Cutaneous vasculitis after COVID-19 vaccination in a 41-year-old maleMehran Pournazari1, Shirin Assar1, Faraneh Farsad2, Dena Mohamadzadeh11Clinical Research Development Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran2 Research Centre of Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

As the Coronavirus Disease 2019 (COVID-19) outbreak spread, evidence has emerged that gender and race would bear a disproportionate impact on the morbimortality of COVID-19. Here, we conducted a retrospective observational study using the TabNet/DATASUS platform of the city of São Paulo. COVID-19 records from March 2020 thru December 2021 were included, and we evaluated the temporal trends of confirmed cases and case fatality rate by gender and ethnicity. Statistical analysis was performed using the R-software and the BioEstat-software, considering p<0.05 significant. From March/2020 to December/2021, 1,315,160 COVID-19 confirmed cases were recorded (57.1% females), and 2,973 deaths were due to COVID-19. Males presented higher median mortality (0.44% vs 0.23%; p<0.05) and ICU admission rates (0.34% vs 0.20%; p<0.05). Men were also associated with a higher risk of death (RR=1.28; p<0.05) and a higher chance of requiring ICU care (RR=1.29; p<0.05). The black ethnicity was associated with a higher risk of death (RR=1.19; p<0.05). White patients were more likely to require ICU admission (RR=1.13; p<0.05), whereas browns were associated with a protective effect (RR=0.86; p<0.05). Further, men presented a higher chance of death than women across the three major ethnic groups: whites (RR=1.33; p<0.05), blacks (RR=1.24; p<0.05), and browns (RR=1.35; p<0.05). In this study of COVID-19 in São Paulo, men were associated with worse outcomes, including in the three major ethnicities in the population. Blacks exhibited a higher risk of death, whites were more likely to require intensive care, and browns were at protection from ICU hospitalization.