Unvaccinated Patients Research Articles

Characteristics of primary care practices by proportion of patients unvaccinated against SARS-CoV-2: a cross-sectional cohort study.

Variations in primary care practices may explain some differences in health outcomes during the COVID-19 pandemic. We sought to evaluate the characteristics of primary care practices by the proportion of patients unvaccinated against SARS-CoV-2. We conducted a population-based, cross-sectional cohort study using linked administrative data sets in Ontario, Canada. We calculated the percentage of patients unvaccinated against SARS-CoV-2 enrolled with each comprehensive-care family physician, ranked physicians according to the proportion of patients unvaccinated, and identified physicians in the top 10% (v. the other 90%). We compared characteristics of family physicians and their patients in these 2 groups using standardized differences. We analyzed 9060 family physicians with 10 837 909 enrolled patients. Family physicians with the largest proportion (top 10%) of unvaccinated patients (n = 906) were more likely to be male, to have trained outside of Canada, to be older, and to work in an enhanced fee-for-service model than those in the remaining 90%. Vaccine coverage (≥ 2 doses of SARS-CoV-2 vaccine) was 74% among patients of physicians with the largest proportion of unvaccinated patients, compared with 87% in the remaining patient population. Patients in the top 10% group tended to be younger and live in areas with higher levels of ethnic diversity and immigration and lower incomes. Primary care practices with the largest proportion of patients unvaccinated against SARS-CoV-2 served marginalized communities and were less likely to use team-based care models. These findings can guide resource planning and help tailor interventions to integrate public health priorities within primary care practices.

Possible causes of morbidity and adverse outcomes of COVID-19 in vaccinated elderly patients

A prospective randomized observational study was conducted in cohorts of vaccinated and unvaccinated patients hospitalized in one of the Moscow hospitals and diagnozed with COVID-19 in the period from 06.23.2021 to 01.05.2022.The purpose of the study was to identify the epidemiological features of COVID-19 in vaccinated people and to present scientifically based data on the need for vaccination and its importance in stopping the epidemic process.Materials and Methods. The samples were studied in comparison for a number of indicators: age, clinical condition at admission, the presence and number of concomitant systemic chronic diseases as well as disease outcomes.Results. It was proven that the risk of COVID-19 morbidity in vaccinated people decreased by 1.5 times, mortality by 1.5 times, and hospitalization due to the severity of the condition by 3.1 times. The mortality risk among vaccinated patients shifted to older age (76.9 years), while among unvaccinated patients, the mortality risk was higher for older people (73.7 years), which indicates an increase in life expectancy of vaccinated people.

Investigation of an mpox outbreak affecting many vaccinated persons in Chicago, IL-March 2023-June 2023.

After months of few mpox cases, an increased number of cases were reported in Chicago during May 2023; predominantly among fully vaccinated patients. We investigated the outbreak scope, differences between vaccinated and unvaccinated patients, and hypotheses for monkeypox virus (MPXV) infection after vaccination. We interviewed patients and reviewed medical records to assess demographic, behavioral, and clinical characteristics, mpox vaccine status, and vaccine administration routes. We evaluated serum antibody levels after infection and compared patient viral genomes with MPXV sequences in available databases. We discussed potential vaccine compromise with partners who manufactured, handled, and administered vaccine associated with breakthrough infections. During March 18-June 27, 2023, we identified 49 mpox cases; 57% of these mpox patients were fully vaccinated (FV). FV patients received both JYNNEOS doses subcutaneously (57%), intradermally (7%), or via heterologous administration (36%). FV patients had more median sex partners (3, IQR=1-4) versus not fully vaccinated (NFV) patients (1, IQR=1-2). Thirty-six of 37 sequenced specimens belonged to lineage B.1.20 of clade IIb MPXV, which did not demonstrate any amino acid changes relative to B.1, the predominant lineage from May 2022. Vaccinated patients demonstrated expected humoral antibody responses; none were hospitalized. No vaccine storage excursions were identified. Approximately 63% of people at risk for mpox in Chicago were FV during this period. Our investigation indicated cases were likely due to frequent behaviors associated with mpox transmission, even with relatively high vaccine effectiveness and vaccine coverage. Cases after vaccination might occur in similar populations.

A Retrospective Study Comparing Mortality Rates between Vaccinated and Unvaccinated Kidney Transplant Recipients

Background: With the emergence of vaccines for COVID-19, mortality and severity of disease have decreased. However, patients with certain comorbidities, such as immunosuppression, CKD, and renal transplant, still have higher mortality rates as compared to the general population. Current data suggests that the risk of developing COVID-19 among transplant patients was reported to be about 5%, which is significantly higher than the risk rate of 0.3% in the general population. Studies utilizing larger sample sizes (i.e., multiple cohorts, sites, hospitals) comparing COVID-19 outcomes among renal transplant patients with a control group are lacking. background: Coronaviruses belong to a family of Viruses that can cause range of illnesses ranging from the common cold, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) (1,2). In 2019 a new Coronavirus was identified and was named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severe Acute Respiratory Syndrome Coronavirus-2 (SARSCoV-2) which belongs to the genus beta-CoV which also includes Severe Acute Respiratory Syndrome CoV (SARS-CoV), and Middle Eastern Respiratory Syndrome CoV (MERS-CoV) (2). World Health Organization (WHO) later announced an alternative name for the disease caused by SARS-CoV-2: CoV disease (COVID-19) (2). As of May 25, 2022 an estimated 524,339,768 cases of COVID-19 were reported to World health organization including 6,281,260 deaths related to COVID globally. However, the disease affects patients with certain risk factors disproportionally. Recent data has shown chronic comorbidities, such as acute kidney injury, COPD, diabetes, hypertension, CVD, cancer, increased D-dimer, along with demographic variables such as male gender, older age, current smoker, and obesity are clinical risk factors for a fatal outcome associated with coronavirus [3]. With the emergence of COVID-19 vaccines, severity and mortality of the disease decreased and has contributed in controlling the pandemic that has claimed so many lives across the globe (4). Even with the emergence of vaccine, the disease continued to claim a disproportionate number of lives, particularly among immunocompromised individuals Objective: The purpose of this descriptive study was to compare the mortality rate between vaccinated and unvaccinated kidney transplant recipients. objective: The purpose of this study is to provide a descriptive overview of clinical outcomes between vaccinated and unvaccinated kidney transplant recipients in a single transplant center in West Texas Methods: Participants were recruited at a community-based transplant clinic in West Texas. Results Among the group of participants who tested positive for COVID-19 between 2020 and 2022, higher mortality rates and longer hospital stays were noted among those unvaccinated (72% unvaccinated had greater than 5-day length of stay vs. 33% vaccinated). method: Retrospective Data was collected from Kidney Transplant Clinic at a Medical Center located in El Paso, Texas. Data was gathered between January 2020 and January 2022 from the transplant database. Data was extrapolated for demographics including age, race, gender. Other data included vaccinated vs. unvaccinated status, comorbidities, immunosuppression status, outcomes such as length of stay in the hospital and mortality rate. A total of 38 patients were included in the study between the year 2020 and 2022. In cases where the patient died, missing data was collected from the next of kin. Inclusion criteria included aged 18 and older, being a kidney transplant recipient (deceased and living) and had a current functioning transplanted kidney. We included all patients who tested positive for COVID-19 during January 2020 to December 2022. Patient whose data could not be obtained since they were deceased and/or did not have next of kin were excluded from the study. Patients were also excluded from the study if their missing data could not be obtained or validated by patient or next of kin. Conclusion: Our study suggests that vaccination against COVID-19 decreases mortality rates in kidney transplant recipients. result: Among the 38 patients included in the data set 94.7% identified as Hispanic vs 5.2% were non-Hispanics and 71% were male vs 28.9% were females. The majority of the patients were vaccinated (71% vs 28.9% non-vaccinated). The data also showed higher rates of death in Unvaccinated population as opposed to vaccinated patients (90.9% vs 14.8%). 72% of unvaccinated transplant recipients had a length of stay greater than 5 days compared to 33% of vaccinated patients. All of the patients evaluated in the cohort had two or more comorbidities such as HTN, atrial fibrillation and DM2 (100%). Among patients included in the cohort 84.2% were deceased renal transplant recipients while 15.7% living renal transplant recipients. Furthermore, increased mortality rates were seen among patients treated with higher induction doses (greater than 350mg). A total of 20 patients in the cohort received greater than 350 mg of induction doses out of which 9 were unvaccinated (45%) and 12 were vaccinated (60%). Out of the 9 unvaccinated patients 8 patients died (88%) while 1 patient survived (11.1). Respiratory failure was the main cause of death among patients that passed away, regardless of vaccine status (90.9% Vaccinated vs 14.8% unvaccinated). conclusion: Large phase 3 clinical trials are still currently underway worldwide to study the effects of vaccine on transplant patient. Our study suggests that vaccination against COVID 19 decreases mortality rates in Kidney Transplant recipient. Our retrospective study compared mortality rates between vaccinated and unvaccinated Kidney transplant recipients in a small clinic setting. It is important to have a large prospective double-blind study on the use of vaccinations in renal transplant recipients would be useful to study the effectiveness on this population.

COVID-19 vaccination: disease status and outcomes of COVID-19 patients admitted in tertiary care hospital in Raigad District of Maharashtra

Background: COVID-19 pandemic had witnessed serious infections and deaths during third wave of the pandemic. This study was designed to analyse the association between severity of disease and patient outcomes with vaccination status of COVID-19 patients. Methods: Retrospective record-based study was conducted among 258 COVID-19 patients from August 2021 to January 2022, during the third wave of the pandemic in a tertiary care hospital. Results: Out of the 258 patients, 42% patients were above 60 years of age 19% were in the age group of 18-30 years. 58% male and 42% female patients. Overall, 50% and 36% patients above 40 years had severe and moderate disease respectively. 52% had mild disease in age group of 18-30 years and this was statistically significant with Chi-square value of 38.85 and p<0.05. 36%, 36% and 28% vaccinated patients had severe, moderate and mild disease respectively. 38%, 40% and 23% unvaccinated patients had severe, moderate and mild disease respectively. The mortality rate was 25%, 32% and 50% among vaccinated, unvaccinated and unknown vaccination status respectively. The mortality rate was 44% in those above 60 years. The survival rates were 90% in patients below 40 years. This difference was statistically significant with Chi-square value of 32.16, p<0.005. The mortality rate was 61%, 16% and 2% with severe, moderate and mild disease respectively. Conclusions: The severity and mortality rate was less in vaccinated patients. This shows that vaccination might be effective in reducing the severity of disease and deaths among COVID-19 patients.

High frequencies of alpha common cold coronavirus/SARS-CoV-2 cross-reactive functional CD4+ and CD8+ memory T cells are associated with protection from symptomatic and fatal SARS-CoV-2 infections in unvaccinated COVID-19 patients.

Cross-reactive SARS-CoV-2-specific memory CD4+ and CD8+ T cells are present in up to 50% of unexposed, pre-pandemic, healthy individuals (UPPHIs). However, the characteristics of cross-reactive memory CD4+ and CD8+ T cells associated with subsequent protection of asymptomatic coronavirus disease 2019 (COVID-19) patients (i.e., unvaccinated individuals who never develop any COVID-19 symptoms despite being infected with SARS-CoV-2) remains to be fully elucidated. This study compares the antigen specificity, frequency, phenotype, and function of cross-reactive memory CD4+ and CD8+ T cells between common cold coronaviruses (CCCs) and SARS-CoV-2. T-cell responses against genome-wide conserved epitopes were studied early in the disease course in a cohort of 147 unvaccinated COVID-19 patients who were divided into six groups based on the severity of their symptoms. Compared to severely ill COVID-19 patients and patients with fatal COVID-19 outcomes, the asymptomatic COVID-19 patients displayed significantly: (i) higher rates of co-infection with the 229E alpha species of CCCs (α-CCC-229E); (ii) higher frequencies of cross-reactive functional CD134+CD137+CD4+ and CD134+CD137+CD8+ T cells that cross-recognized conserved epitopes from α-CCCs and SARS-CoV-2 structural, non-structural, and accessory proteins; and (iii) lower frequencies of CCCs/SARS-CoV-2 cross-reactive exhausted PD-1+TIM3+TIGIT+CTLA4+CD4+ and PD-1+TIM3+TIGIT+CTLA4+CD8+ T cells, detected both ex vivo and in vitro. These findings (i) support a crucial role of functional, poly-antigenic α-CCCs/SARS-CoV-2 cross-reactive memory CD4+ and CD8+ T cells, induced following previous CCCs seasonal exposures, in protection against subsequent severe COVID-19 disease and (ii) provide critical insights into developing broadly protective, multi-antigen, CD4+, and CD8+ T-cell-based, universal pan-Coronavirus vaccines capable of conferring cross-species protection.

Impact of COVID-19 vaccination on liver transplant recipients. Experience in a reference center in Mexico.

COVID-19 vaccination has proved to be effective to prevent symptomatic infection and severe disease even in immunocompromised patients including liver transplant patients. We aim to assess the impact of COVID-19 vaccination on the mortality and development of severe and critical disease in our center. A retrospective cohort study of LT patients in a reference center between March 2020 and February 2022. Demographic data, cirrhosis etiology, time on liver transplantation, immunosuppressive therapies, and vaccination status were recorded at the time of diagnosis. Primary outcome was death due to COVID-19, and secondary outcomes included the development of severe COVID-19 and intensive care unit (ICU) requirement. 153 of 324 LT recipients developed COVID-19, in whom the main causes of cirrhosis were HCV infection and metabolic-associated fatty liver disease. The vaccines used were BNT162b2 (48.6%), ChAdOx1 nCoV-19 (21.6%), mRNA-1273 vaccine (1.4%), Sputnik V (14.9%), Ad5-nCoV-S (4.1%) and CoronaVac (9.5%). Case fatality and ICU requirement risk were similar among vaccinated and unvaccinated LT patients (adjusted relative case fatality for vaccinated versus unvaccinated of 0.68, 95% CI 0.14-3.24, p = 0.62; adjusted relative risk [aRR] for ICU requirement of 0.45, 95% CI 0.11-1.88, p = 0.27). Nonetheless, vaccination was associated with a lower risk of severe disease (aRR for severe disease of 0.32, 95% CI 0.14-0.71, p = 0.005). Vaccination reduces the risk of severe COVID-19 in LT patients, regardless of the scheme used. Vaccination should be encouraged for all.

Delayed Antibody Response in the Acute Phase of Infection Is Associated with a Lower Mental Component of Quality of Life in Survivors of Severe and Critical COVID-19.

Background: The long-term sequelae of coronavirus disease 2019 (COVID-19) significantly affects quality of life (QoL) in disease survivors. Delayed development of the adaptive immune response is associated with more severe disease and a worse prognosis in COVID-19. The effects of delayed immune response on COVID-19 sequelae and QoL are unknown. Methods: We conducted a prospective study to assess the relationship between the delayed antibody response in the acute phase of infection in naïve unvaccinated patients suffering from severe or critical COVID-19 and their QoL 12 months after hospital discharge. The 12-item Short Form Survey (SF-12) questionnaire was used for assessment of QoL. The SF-12 evaluates both mental and physical components of QoL, incorporating a mental component score (MCS-12) and a physical component score (PCS-12). A delayed antibody response was defined as testing negative for anti-spike SARS-CoV-2 antibodies at the time of hospital admission. Results: The study included 274 patients (154 men and 120 women). Of the enrolled patients, 144 had a delayed immune response. These patients had a significantly lower MCS-12 (p = 0.002), but PCS-12 (p = 0.397) was not significantly different at the 12-month follow-up compared to patients with positive anti-spike SARS-CoV-2 antibodies. The MCS-12 at the time of follow-up was negatively associated with delayed antibody response irrespective of possible confounders (p = 0.006; B = 3.609; ηp2 = 0.035; 95% CI = 1.069-6.150). An MSC-12 below 50 points at the time of follow-up was positively associated with delayed antibody response (p = 0.001; B = 1.092; OR = 2.979; 95% CI = 1.554-5.711). Conclusions: This study confirmed that, in patients with severe and critical COVID-19, a negative result for anti-spike SARS-CoV-2 antibodies at the time of hospital admission is associated with a lower mental component of QoL in unvaccinated patients naïve to COVID-19 one year after hospital discharge.

Promotion of Influenza Vaccination in the Emergency Department

BackgroundInfluenza vaccine uptake is low among underserved populations whose primary health care access occurs in emergency departments. We sought to determine whether implementation of two interventions would increase 30-day influenza vaccine uptake in unvaccinated patients in the emergency department.MethodsThis three-group, prospective, cluster-randomized controlled trial compared two interventions with a control group in noncritically ill, adult patients in the emergency department who were not vaccinated for influenza in the current vaccine season. The unit of randomization was individual calendar days. Participants received either Intervention M (an influenza vaccine messaging platform consisting of a video, one-page flyer, and scripted message, followed by a vaccine acceptance question and provider notification if participants indicated vaccine acceptance), Intervention Q (no messaging but the vaccine acceptance question and provider notification), or control (usual care/no intervention). The primary outcome was receipt of an influenza vaccine at 30 days ascertained by electronic health record review and telephone follow-up, comparing the Intervention M group with the control group. Secondary outcomes included comparisons of 30-day vaccine uptake in Intervention Q versus control and Intervention M versus Intervention Q.ResultsBetween October 2022 and February 2023, a total of 767 trial participants were enrolled at six emergency departments in five U.S. cities. Median age was 46 years; 353 (46%) participants were female, 274 (36%) were African American, and 158 (21%) were Latinx; 126 (16%) lacked health insurance, and 244 (32%) lacked primary care. The Intervention M, Intervention Q, and control groups had 30-day vaccine uptakes of 41%, 32%, and 15%, respectively (P<0.0001 for Intervention M vs. control). Comparing Intervention M versus Intervention Q, the adjusted difference in 30-day vaccine uptake was 8.7 percentage points (95% confidence interval, −0.1 to 17.6 percentage points).ConclusionsImplementation of influenza vaccine messaging platforms (video clips, printed materials, and verbal scripts) improved 30-day vaccine uptake among unvaccinated patients in the emergency department. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT05836818.)

Epidemiology, clinical features and outcomes of hospitalized patients with COVID-19 by vaccination status: a multicenter historical cohort study

IntroductionCOVID-19 disease resulted in over six million deaths worldwide. Although vaccines against SARS-CoV-2 demonstrated efficacy, breakthrough infections became increasingly common. There is still a lack of data regarding the severity and outcomes of COVID-19 among vaccinated compared to unvaccinated individuals.MethodsThis was a historical cohort study of adult COVID-19 patients hospitalized in five Ascension hospitals in southeast Michigan. Electronic medical records were reviewed. Vaccine information was collected from the Michigan Care Improvement Registry. Data were analyzed using Student’s t-test, analysis of variance, the chi-squared test, the Mann-Whitney and Kruskal-Wallis tests, and multivariable logistic regression.ResultsOf 341 patients, the mean age was 57.9 ± 18.3 years, 54.8% (187/341) were female, and 48.7% (166/341) were black/African American. Most patients were unvaccinated, 65.7%, 8.5%, and 25.8% receiving one dose or at least two doses, respectively. Unvaccinated patients were younger than fully vaccinated (p = 0.001) and were more likely to be black/African American (p = 0.002). Fully vaccinated patients were 5.3 times less likely to have severe/critical disease (WHO classification) than unvaccinated patients (p < 0.001) after controlling for age, BMI, race, home steroid use, and serum albumin levels on admission. The case fatality rate in fully vaccinated patients was 3.4% compared to 17.9% in unvaccinated patients (p = 0.003). Unvaccinated patients also had higher rates of complications.ConclusionsPatients who were unvaccinated or partially vaccinated had more in-hospital complications, severe disease, and death as compared to fully vaccinated patients. Factors associated with severe COVID-19 disease included advanced age, obesity, low serum albumin, and home steroid use.

Post-acute COVID-19 syndrome in previously hospitalized patients.

With the prolongation of the COVID-19 pandemic, more individuals are experiencing sequelae after COVID-19 infection, also known as post-acute COVID-19 syndrome (PCS). The aims of this study were to describe the prevalence and characteristics of PCS symptoms such as fatigue, anxiety, and depression and to compare these symptoms according to participant characteristics in patients who had been previously hospitalized due to COVID-19. A descriptive cross-sectional study design was used. We included 114 individuals who had been hospitalized for COVID-19 and were discharged from the hospital at least 4 weeks before. Symptoms were assessed using the Fatigue Severity Scale, the Hospital Anxiety-Depression Scale, and the PCS symptom questionnaire developed by the authors. We used descriptive statistics, the Student's t-test, the Wilcoxon rank-sum test, and the Kruskal-Wallis test for statistical analyses. The most prevalent symptoms were anxiety (66.7%), fatigue (64.0%), headache (57.9%), and concentration or memory difficulties (57.9%). Concentration or memory difficulties and sleep disturbances had the highest mean frequency. Concentration or memory difficulties were rated with the highest mean severity, and cough, loss of taste, and muscle and joint pain had the highest mean distress scores. Female participants, individuals hospitalized for more than 2 weeks, individuals discharged more than 9 months ago, unvaccinated patients, and those who tried at least one symptom relief method reported higher symptom distress. The findings of this investigation into the frequency, severity, and distress of symptoms shed light on the identification of post-COVID symptoms in detail. To objectively evaluate and comprehend the symptom trajectories of PCS, prospective studies about the development of symptom assessment tools and studies with a longitudinal design should be conducted. A substantial number of respondents reported numerous symptoms and expressed symptom distress; therefore, the development of nursing interventions and treatments to alleviate PCS symptoms is crucial.

Factors associated with the worsening of COVID-19 symptoms among cohorts in community- or home-isolation care in southern Thailand.

This study aimed to investigate factors associated with time-to-referral due to worsening symptoms in patients with laboratory-confirmed COVID-19 in southern Thailand. While underlying diseases have been evaluated to assess COVID-19 severity, the influence of vaccinations and treatments is also crucial. A cohort of 8,638 patients quarantined in home or community isolation with laboratory-confirmed COVID-19 was analyzed. Survival analysis and the Cox proportional hazard ratio were employed to assess factors influencing time-toreferral. Age ≥ 60 years, neurologic disorders, cardiovascular disease, and human immunodeficiency virus infection were identified as significant risk factors for severe COVID-19 referral. Patients who received full- or booster-dose vaccinations had a lower risk of experiencing severe symptoms compared to unvaccinated patients. Notably, individuals vaccinated during the Omicron-dominant period had a substantially lower time-to-referral than those unvaccinated during the Delta-dominant period. Moreover, patients vaccinated between 1 and 6 months prior to infection had a significantly lower risk of time-to-referral than the reference group. These findings demonstrate early intervention in high-risk COVID-19 patients and the importance of vaccination efficacy to reduce symptom severity. The study provides valuable insights for guiding future epidemic management strategies and optimising patient care during infectious disease outbreaks.

Acceptance, safety, and immunogenicity of a booster dose of inactivated SARS-CoV-2 vaccine in patients with primary biliary cholangitis

Inactivated coronavirus disease 2019 (COVID-19) vaccines showed impaired immunogenicity in some autoimmune diseases, but it remains unclear in primary biliary cholangitis (PBC). This study aimed to explore the antibody response to the inactivated COVID-19 vaccine in individuals with PBC, as well as to evaluate coverage, safety, and attitudes toward the COVID-19 vaccine among them. Two cohorts of patients with PBC were enrolled in this study. One cohort was arranged to evaluate the immunogenicity of the inactivated COVID-19 vaccine, another cohort participated in an online survey. The titers of the anti-receptor-binding domain (RBD)-specific immunoglobulin G (IgG), neutralizing antibody (NAb) toward severe acute respiratory syndrome coronavirus 2 wild-type, and NAb toward Omicron BA.4/5 subvariants were detected to assess antibody response from the vaccine. After booster vaccination for more than six months, patients with PBC had significantly lowered levels of anti-RBD-specific IgG compared to HCs, and the inhibition rates of NAb toward wild-type also declined in individuals with PBC. The detected levels of NAb toward Omicron BA.4/5 were below the positive threshold in patients with PBC and HCs. Laboratory parameters did not significantly correlate with any of the three antibodies. The online survey revealed that 24% of patients with PBC received three COVID-19 vaccines, while 63% were unimmunized. Adverse effect rates after the first, second, and third vaccine doses were 6.1%, 10.3%, and 9.5%, respectively. Unvaccinated patients with PBC were more worried about the safety of the vaccine than those who were vaccinated (P = 0.004). As a result, this study fills the immunological assessment gap in patients with PBC who received inactivated COVID-19 vaccines.

Prolonged exposure to lung-derived cytokines is associated with activation of microglia in patients with COVID-19.

Survivors of pneumonia, including SARS-CoV-2 pneumonia, are at increased risk for cognitive dysfunction and dementia. In rodent models, cognitive dysfunction following pneumonia has been linked to the systemic release of lung-derived pro-inflammatory cytokines. Microglia are poised to respond to inflammatory signals from the circulation, and their dysfunction has been linked to cognitive impairment in murine models of dementia and in humans. We measured the levels of 55 cytokines and chemokines in bronchoalveolar lavage fluid and plasma from a cohort of 341 patients with respiratory failure and 13 healthy control patients, including 93 unvaccinated patients with COVID-19 and 203 patients with other causes of pneumonia. We flow-cytometry sorted neuroimmune cells from postmortem brain tissue from 5 patients who died from COVID-19 and 3 patients who died from other causes for single-cell RNA-sequencing. Microglia from patients with COVID-19 exhibited a transcriptomic signature suggestive of their activation by circulating pro-inflammatory cytokines. Peak levels of pro-inflammatory cytokines were similar in patients with pneumonia irrespective of etiology, but cumulative cytokine exposure was higher in patients with COVID-19. Treatment with corticosteroids reduced expression of COVID-19-specific cytokines. Prolonged lung inflammation results in sustained elevations in circulating cytokines patients with SARS-CoV-2 pneumonia compared to those with pneumonia secondary to other pathogens. Microglia from patients with COVID-19 exhibit transcriptional responses to inflammatory cytokines. These findings support data from rodent models causally linking systemic inflammation with cognitive dysfunction in pneumonia and support further investigation into the role of microglia in pneumonia-related cognitive dysfunction. SCRIPT U19AI135964.

Effectiveness of COVID-19 vaccines against severe outcomes in cancer patients: Real-world evidence from self-controlled risk interval and retrospective cohort studies

BackgroundThe effectiveness of COVID-19 vaccines is generally reduced in cancer patients compared to the general population. However, there are only a few studies that compare the relative risk of breakthrough infections and severe COVID-19 outcomes in fully vaccinated cancer patients versus their unvaccinated counterparts. MethodsTo assess the effectiveness of COVID-19 vaccines in cancer patients, we employed (1) a self-controlled risk interval (SCRI) design, and (2) a retrospective matched cohort design. A SCRI design was used to compare the risk of breakthrough infection in vaccinated cancer patients during the period immediately following vaccination (“control window”) and the period in which immunity is achieved (“exposure windows”). The retrospective matched cohort design was used to compare the risk of severe COVID-19 outcomes between vaccinated and unvaccinated cancer patients. For both studies, data were extracted from the Korea Disease Control and Prevention Agency-COVID-19-National Health Insurance Service cohort, including demographics, medical history, and vaccination records of all individuals confirmed with COVID-19. We used conditional Poisson regression to calculate the incidence rate ratio (IRR) for breakthrough infection and Cox regression to estimate the hazard ratio (HR) for severe outcomes. ResultsOf 14,448 cancer patients diagnosed with COVID-19 between October 2020 and December 2021, a total of 217 and 3996 cancer patients were included in the SCRI and cohort study respectively. While the risk of breakthrough infections, measured by the incidence rate in the control and exposure windows, did not show statistically significant difference in vaccinated cancer patients (IRR=0.88, 95% CI: 0.64–1.22), the risk of severe COVID-19 outcomes was significantly lower in vaccinated cancer patients compared to those unvaccinated (HR=0.27, 95% CI: 0.22–0.34). ConclusionCOVID-19 vaccines significantly reduce the risk of severe outcomes in cancer patients, though their efficacy against breakthrough infections is less evident.

Early treatment with fluvoxamine, bromhexine, cyproheptadine, and niclosamide to prevent clinical deterioration in patients with symptomatic COVID-19: a randomized clinical trial

Repurposed drugs with host-directed antiviral and immunomodulatory properties have shown promise in the treatment of COVID-19, but few trials have studied combinations of these agents. The aim of this trial was to assess the effectiveness of affordable, widely available, repurposed drugs used in combination for treatment of COVID-19, which may be particularly relevant to low-resource countries. We conducted an open-label, randomized, outpatient, controlled trial in Thailand from October 1, 2021, to June 21, 2022, to assess whether early treatment within 48-h of symptoms onset with combinations of fluvoxamine, bromhexine, cyproheptadine, and niclosamide, given to adults with confirmed mild SARS-CoV-2 infection, can prevent 28-day clinical deterioration compared to standard care. Participants were randomly assigned to receive treatment with fluvoxamine alone, fluvoxamine+bromhexine, fluvoxamine+cyproheptadine, niclosamide+bromhexine, or standard care. The primary outcome measured was clinical deterioration within 9, 14, or 28 days using a 6-point ordinal scale. This trial is registered with ClinicalTrials.gov (NCT05087381). Among 1900 recruited, a total of 995 participants completed the trial. No participants had clinical deterioration by day 9, 14, or 28 days among those treated with fluvoxamine plus bromhexine (0%), fluvoxamine plus cyproheptadine (0%), or niclosamide plus bromhexine (0%). Nine participants (5.6%) in the fluvoxamine arm had clinical deterioration by day 28, requiring low-flow oxygen. In contrast, most standard care arm participants had clinical deterioration by 9, 14, and 28 days. By day 9, 32.7% (110) of patients in the standard care arm had been hospitalized without requiring supplemental oxygen but needing ongoing medical care. By day 28, this percentage increased to 37.5% (21). Additionally, 20.8% (70) of patients in the standard care arm required low-flow oxygen by day 9, and 12.5% (16) needed non-invasive or mechanical ventilation by day 28. All treated groups significantly differed from the standard care group by days 9, 14, and 28 (p<0.0001). Also, by day 28, the three 2-drug treatments were significantly better than the fluvoxamine arm (p<0.0001). No deaths occurred in any study group. Compared to standard care, participants treated with the combination agents had significantly decreased viral loads as early as day 3 of treatment (p<0.0001), decreased levels of serum cytokines interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) as early as day 5 of treatment, and interleukin-8 (IL-8) by day 7 of treatment (p<0.0001) and lower incidence of post-acute sequelae of COVID-19 (PASC) symptoms (p<0.0001). 23 serious adverse events occurred in the standard care arm, while only 1 serious adverse event was reported in the fluvoxamine arm, and zero serious adverse events occurred in the other arms. Early treatment with these combinations among outpatients diagnosed with COVID-19 was associated with lower likelihood of clinical deterioration, and with significant and rapid reduction in the viral load and serum cytokines, and with lower burden of PASC symptoms. When started very soon after symptom onset, these repurposed drugs have high potential to prevent clinical deterioration and death in vaccinated and unvaccinated COVID-19 patients. Ped Thai Su Phai (Thai Ducks Fighting Danger) social giver group.

COVID-19 Clinical Features and Outcome in Italian Patients Treated with Biological Drugs Targeting Type 2 Inflammation.

This is a multicentric investigation involving two Italian centers that examined the clinical course of COVID-19 in patients receiving biological therapy targeting type 2 inflammation and those not receiving biologicals. Since the beginning of the COVID-19 pandemic, the management of respiratory and allergic disorders and the potential impact of biological therapy in the most severe forms has been a point of uncertainty. Our multicentric investigation aimed to compare the clinical course of COVID-19 and the impact of vaccination in an Italian cohort of patients with atopic disorders caused by a type 2 inflammation, such as eosinophilic asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU). A questionnaire was given to patients coming to our outpatient clinic for the first evaluation or follow-up visit, asking for the clinical characteristics of the infection, the ongoing therapy during the infection, any relevant change, and the patient's vaccination status. We enrolled 132 atopic patients from two Italian centers; 62 patients were on biological therapy at the time of infection (omalizumab 31%, mepolizumab 26%, benralizumab 19%, and dupilumab 24%). The median age was 56 (IQR 22.8) for patients on biologicals and 48 (IQR 26.5) for those not on biologicals (p = 0.028). The two groups were comparable in terms of sex, body mass index (BMI), smoking history, and systemic oral corticosteroid use (OCS). There were no significant differences in non-biological therapy and comorbidity between the two groups. The patients not on biological therapy had a prevalence of 87% for asthma, 52% for CRSwNP, 10% for CSU, and 6% for AD. The patients on biologicals had a prevalence of 93% for asthma, 17% for CRSwNP, and 10% for CSU. In our work, we observed that mAbs targeting type 2 inflammation in patients with COVID-19 appeared to be safe, with no worsening of symptoms, prolongation of infection, or increase in hospitalizations. Between the two groups, there were no significant differences in the duration of swab positivity (p = 0.45) and duration of symptoms (p = 0.38). During COVID-19, patients on biologicals experienced a significant increase in common cold-like symptoms (p = 0.038), dyspnea (p = 0.016), and more, but not significant, asthma exacerbations, with no significant differences between the different biologicals. Regarding the vaccination status, we observed that there was an increased number of hospitalizations among unvaccinated patients in both groups, although the difference did not reach statistical significance. No patients on biologicals reported safety issues or adverse effects associated with the use of biological treatments during COVID-19. Our investigation showed that mAbs against type 2 inflammation given during Coronavirus Disease 2019 are safe and do not impact the clinical course or main outcomes. Therefore, we found no signals suggesting that anti-Th2 biological therapy should be discontinued during SARS-CoV-2 infection. Controlled studies and analysis, including data from registries and real-life studies, are required to draw firm conclusions regarding the safety or possible advantages that anti-type 2 mAbs could offer in particular clinical contexts, such as infections.

COVID-19 vaccination rate in patients admitted to the Immunology and Allergy Outpatient Clinic

Aim&#x0D; Misinformation, lack of awareness, and beliefs about vaccines can cause hesitations about vaccines and affect the rate of vaccination. We aimed to reveal the vaccination rates against coronavirus disease-19 (COVID-19) (vaccine types and dose), and the reasons for not being vaccinated in patients admitted to the immunology and allergy outpatient clinic. In addition, we aimed to find out whether allergic reactions were observed in vaccinated patients.&#x0D; Methods&#x0D; The history of COVID-19 and vaccination of patients admitted to the Immunology and Allergy Outpatient Clinic between December 2021 and February 2022 were evaluated retrospectively.&#x0D; Results&#x0D; In our study, which included 451 patients, the median age of the patients was 35 (range 18-82), and 61.2% were women. 16.9% of the patients admitted to the immunology and allergy outpatient clinic were never vaccinated, while the rate of those who did not receive two doses of vaccine was 26.6%. The top three reasons for not being vaccinated were fear of allergies, fear of adverse effects, and distrust of the vaccine, respectively. Unvaccinated patients were younger, which is statistically significant. Vaccination rate was found to be lower in drug allergy and immunodeficiencies compared to other disease groups. &#x0D; Conclusion&#x0D; Understanding the causes of vaccine hesitations and increasing the vaccination rate by organizing public health campaigns is an important point in the control of the pandemic. Despite being rare, allergic reactions can be observed with COVID-19 vaccines. Therefore, immunologists and allergists play an important role in the COVID-19 vaccine program.

The effect of vaccination against the COVID-19 on the course and outcomes of a new coronavirus infection: a retrospective analysis of laboratory and clinical indicators of hospitalized patients

BACKGROUND: The Gam-COVID-Vac vaccine was proven effective in preventing the severe course and adverse outcomes of COVID-19 during different periods of the pandemic. However, the effect of vaccination on laboratory marker levels in hospitalized patients during the spread of the omicron variant of SARS-CoV-2 has not been sufficiently studied.&#x0D; AIM: To assess the effect of vaccination on the severity and outcomes of COVID-19 in hospitalized patients during the dominance of the SARS-CoV-2 omicron variant in Russia.&#x0D; MATERIALS AND METHODS: This case–control study included adult patients diagnosed with COVID-19 (U07.1) and hospitalized in infectious hospitals in Moscow between February 1, 2022, and July 31, 2022 (n=119). The main group included individuals vaccinated with two doses of Sputnik V vaccine (n=59). The control group included individuals who were not vaccinated (n=60). The median patient age was 66 [interquartile range, 41–66] years, and 58.8% were female. The chi-square test for categorical variables and the Mann–Whitney test for continuous variables were used for the analysis. P-values 0.05 were considered statistically significant.&#x0D; RESULTS: Viral pneumonia was less likely to develop in the vaccinated group than in the unvaccinated group (46.7% and 18.6%, respectively, p = 0.007). The proportion of patients without lung damage (0 CT-severity scores) in the vaccinated group (72.0%) was significantly higher than that in the unvaccinated group (42.9%) (p=0.003). In the vaccinated group, the levels of C-reactive protein on admission were lower (29.1 [7.4–68.6] mg/L and 75.1 [32.4–104.0] mg/L, p 0.001), and the highest level was recorded during hospitalization (38.2 [12.0–84.0] mg/L and 92.2 [45.3–137.4] mg/L, p 0.001). The D-dimer levels before discharge were lower in the group of patients vaccinated 6 months ago than in the unvaccinated group (157.0 [107.0–297.0] ng/mL and 316.0 [125.0–556.0] ng/mL, respectively, p = 0.014). The frequency of deaths in the control group (11.7%) was 6.9 times higher than that in the main group (1.7%) (p = 0.030).&#x0D; CONCLUSIONS: Completion of the primary vaccination course of Sputnik V vaccine resulted in lower levels of prognostic markers of severe COVID-19 (C-reactive protein and D-dimer) and a decrease in the frequency of pulmonary and fatal outcomes than in the unvaccinated group during the dominance of the omicron variant of SARS-CoV-2.

Association of COVID-19 vaccination with duration of hospitalization in older adults in Hong Kong

IntroductionThe association between COVID-19 vaccination and length of hospital stay may provide further insight into vaccination benefits, but few studies have investigated such associations in detail. We aimed to investigate the association between COVID-19 vaccination and length of hospital stay in COVID-19 patients during Omicron waves in Hong Kong, and explore potential predictors. MethodsThis retrospective cohort study was conducted on local patients aged ≥60 years who were admitted due to COVID-19 infection in Hong Kong in 2022, from 1 February to 22 November, and with 28 days of follow-up since admission. The exposure was either not vaccinated; or having received 2/3/4 doses of CoronaVac (Sinovac); or 2/3/4 doses of BNT162b2 (BioNTech/Fosun Pharma/Pfizer). Length of stay in hospital was the main outcome. Accelerated failure time models were used to quantify variation in hospital stay for vaccinated compared with unvaccinated patients, accounting for age, sex, comorbidity, type of vaccine and number of doses received, care home residence and admission timing; stratified by age groups and epidemic waves. ResultsThis study included 32,398 patients aged 60 years and above for main analysis, their median (IQR) age was 79 (71–87) years, 53% were men, and 40% were unvaccinated. The patients were stratified by confirmation prior to or since 23 May 2022, resulting in a sample size of 15,803 and 16,595 in those two waves respectively. Vaccinated patients were found to have 13–39% shorter hospital stay compared to unvaccinated patients. More vaccine doses received were associated with shorter hospital stay, and BNT162b2 recipients had slightly shorter hospital stays than CoronaVac recipients. ConclusionVaccination was associated with reduced hospital stay in breakthrough infections. Increased vaccination uptake in older adults may improve hospital bed turnover and public health outcomes especially during large community epidemics.