The coronavirus disease of 2019 (COVID-19) vaccination has reduced the severity of illness and hospitalization rates associated with the virus. However, pregnant and lactating refugee women often have lower vaccination rates, which are influenced by limited access to healthcare, cultural barriers, and misinformation. This study, guided by the Positive Deviance Framework, examines the factors that promoted COVID-19 vaccination among pregnant and lactating refugee women.

Cultural Health Navigators conducted in-depth interviews with pregnant and lactating refugee women recruited from a large federally qualified health center who received COVID-19 vaccines.

This qualitative study included 30 participants, stratified by language groups and representing diverse educational backgrounds and lengths of residence in the United States. Thematic analysis of the interviews revealed factors such as fear of COVID-19, emotional relief following vaccination, trust in healthcare providers and scientific evidence, and support from family and Cultural Health Navigators.

The findings highlight the importance of culturally sensitive communication and trust-building in promoting vaccination rates among pregnant and lactating refugee women. Trust in healthcare providers, scientific evidence, and support from family and Cultural Health Navigators played a key role in overcoming vaccination barriers. Tailored strategies and supportive interventions can enhance COVID-19 vaccination uptake in this population. Further research in larger, diverse populations is needed to identify additional strategies for improving vaccination rates among refugee women.

Many drugs can induce liver injury; however, vaccine-induced liver injury is a rare phenomenon. SARS-CoV-2 messenger RNA (mRNA) vaccines are now widely administered, and clinical evidence of liver injury has been reported.

To characterize the histologic features of SARS-CoV-2 mRNA vaccine-associated liver injury.

Thirteen liver biopsies from 12 patients with elevated liver enzymes clinically favored to be secondary to SARS-CoV-2 mRNA vaccine were identified between 2021 and 2022. Demographics, clinical information, and histologic features of liver biopsies were reviewed.

All patients (median age, 58 years; M:F = 4:8) received at least 1 dose of SARS-CoV-2 mRNA vaccines (7 Pfizer and 5 Moderna). Four patients had a history of liver disease. Nine patients developed symptoms between 1 day and 2 months after receiving the vaccine dose. Viral serologies were negative. Drug-induced liver injury was thought to be less likely clinically in the 3 patients who had started new medications. Autoimmune antibodies were detected in 9 patients. Moderate to severe active hepatitis was the dominant histologic pattern of injury (9 of 13 biopsies; 69%). Resolving hepatitis, cholestatic hepatitic injury, and bile duct injury were identified in 1 biopsy each. All patients recovered spontaneously or with steroid therapy, except one patient who developed autoimmune hepatitis.

Moderate to severe active hepatitis is commonly observed in SARS-CoV-2 mRNA vaccine-associated liver injury, and female patients may be more susceptible to injury. Liver injury resolves spontaneously or with steroid treatment. In rare cases, these vaccines may trigger an underlying immune condition.

Schizophrenia is associated with substantial physical and psychiatric comorbidities that increase the risk of severe outcomes in COVID-19 infection. However, few studies have examined the differences in care and outcomes among people with schizophrenia throughout the pandemic. We hypothesized that rates of in-hospital mortality, admission to the intensive care unit (ICU), and length of stay differed among people with and without schizophrenia.

We conducted a population-based retrospective cohort study using administrative health data from Ontario, Canada, which included individuals hospitalized for COVID-19 between February 2020 and October 2023. We compared mortality, ICU admission, and length of stay using regression models adjusted for age, sex, comorbidities, vaccination status, and sociodemographic characteristics.

We evaluated 66 959 hospital admissions, 4.3% (2884) of which involved people with schizophrenia. People with schizophrenia had a significantly decreased rate of ICU admission (adjusted Odds Ratio [OR]: 0.74 [0.67, 0.82]), a longer length of stay (adjusted RR: 1.25 [1.21, 1.30]), but a similar risk of mortality (adjusted OR: 1.09 [0.98, 1.22]) as people without schizophrenia. Age modified the relationship between schizophrenia and ICU admission. People with schizophrenia aged 60-75 were substantially less likely to be admitted to the ICU relative to those without (18.4% vs 26.5%, P < .001).

Our findings underscore disparities in care among people with and without schizophrenia. These disparities vary by age and suggest that people with schizophrenia may not be receiving the same level of care as people without schizophrenia hospitalized for COVID-19.

To explore the association between perioperative SARS-CoV-2 infection and the postoperative complications during the breakout of the Omicron epidemic wave.

Observational retrospective cohort study. Multivariable logistic regression was performed to explore the association between the duration from surgery to COVID-19 diagnosis and the likelihood of postoperative complications.

A general hospital in China.

7927 patients aged 18 years and older who underwent surgical treatment between 1 December 2022 and 28 February 2023.

The outcome was a composite of postoperative adverse events that occurred within the initial 30 postoperative days.

Of all patients, 420 (11.76%) experienced postoperative complications. Compared with No COVID-19, preoperative COVID-19 within 1 week (pre-1w) exhibited a high risk of postoperative complications (adjusted OR (aOR), 2.67; 95% CI 1.50 to 4.78), followed by patients with pre-2w (aOR, 2.14; 95% CI 1.20 to 3.80). For patients with postoperative COVID-19 within 1 week (post-1w), the aOR was 2.48 (95% CI 1.48 to 4.13), followed by patients with post-2w (aOR 1.95; 95% CI 1.10 to 3.45), and those with post-3w (aOR 2.25; 95% CI 1.27 to 3.98). The risks of postoperative complications decreased roughly with the increase of the time interval between the surgery date and SARS-CoV-2 infection. Stratification analyses suggested that perioperative COVID-19 increased the risk of postoperative complications in older patients, smokers, those with comorbidities or experiencing moderate or severe COVID-19 symptoms.

Our findings reveal a significant time-dependent relationship between perioperative COVID-19 and postoperative complications, highlighting the importance of tailored preoperative risk evaluations, enhanced postoperative surveillance, and the implementation of effective postoperative COVID-19 prevention measures.

ChiCTR2300072473.

COVID-19-associated acute respiratory distress syndrome (ARDS) has challenged healthcare systems, initially resembling classical ARDS but later recognized as distinct. Unique features such as endothelial injury, microthrombosis, and dysregulated inflammation influenced treatment efficacy. Understanding its evolution is key to optimizing therapy and improving outcomes.

This review synthesizes current evidence on COVID-19-associated ARDS, covering epidemiology, pathophysiology, clinical phenotypes, and treatments. It explores the shift from L and H phenotypes to a refined disease model and highlights key therapies, including corticosteroids, immunomodulators, prone positioning, ECMO, and vaccination's impact on severity and ARDS incidence.

At the onset of the COVID-19 pandemic in December 2019, uncertainty was overwhelming. Early clinical guidelines relied on case reports and small case series, offering only preliminary insights into disease progression and management. Despite the initial chaos, the scientific community launched an unprecedented research effort, with over 11,000 clinical trials registered on ClinicalTrials.gov investigating COVID-19 treatments. Several evidence-based strategies emerged as gold standards for managing COVID-19-associated acute respiratory distress syndrome, surpassing prior approaches. The pandemic exposed vulnerabilities in global healthcare, reshaped modern medicine, accelerated innovation, and reinforced the essential role of evidence-based practice in critical care and public health policy.

Since the remarkable breakthrough of COVID-19 mRNA vaccines, lipid nanoparticles (LNPs) have gained substantial attention as the most cutting-edge clinical formulations for mRNA delivery. PEGylated lipid (PEG-lipid) has been regarded as an essential constituent of LNPs that helps to prolong their systemic circulation by preventing particle aggregation in the blood and sequestration by the mononuclear phagocyte system. Herein, we synthesized a series of mRNA-loaded nanoparticles by replacing ALC-0159 (a PEG-lipid used in the Comirnaty formulation) with amphiphilic PEG-polycarbonate diblock copolymers (PC-HNPs). Interestingly, variations of polycarbonate block length and structure significantly influenced mRNA encapsulation efficiency, transfection potency, colloidal stability, and PEG shedding rate of PC-HNPs. In vivo and ex vivo bioluminescence imaging revealed that upon subcutaneous administration in mice, the leading candidate PC3-HNP achieved lymph node accumulation comparable to that of the conventional ALC-0159-based LNP formulation while avoiding undesirable liver accumulation. Our findings may provide valuable information for the construction of next-generation nanocarriers for effective mRNA delivery.

Amid changing variant and immunity landscapes since early in the coronavirus disease 2019 (COVID-19) pandemic, common COVID-19 symptoms need better understanding in relation to prior immunity or infecting variant.

American Red Cross blood donors were surveyed during February-April 2022 about prior COVID-19 vaccinations and symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Donations were tested for anti-nucleocapsid antibodies to inform infection history. Restricting analysis to donors with survey-reported infections during the Omicron BA.1-predominant period (19 December 2021 through 19 March 2022), we used multivariable logistic regression to compare symptoms by existing immunity from prior infection or vaccination. Restricting analysis to those with no existing immunity, we compared symptoms by variant-predominant period of their first reported infection (BA.1 vs before).

Among 9505 donors with a BA.1-predominant period infection, donors with prior infection (n = 1115), vaccination (n = 5888), or both (n = 1738) were less likely than those without prior immunity (n = 764) to report loss of taste or smell, lower respiratory tract, constitutional, or gastrointestinal symptoms and more likely to report upper respiratory tract symptoms. Stronger associations followed recent prior infection, vaccination, or more vaccine doses. Among 8539 donors without prior immunity, those with survey-reported infections during the BA.1-predominant period (n = 764) were less likely to report loss of taste or smell, or lower respiratory tract symptoms than those with infections before this period (n = 7775).

Our data suggest that both prior immunity and Omicron predominance redistributed COVID-19 symptoms toward upper respiratory tract presentations and likely both contributed to a decrease in COVID-19 severity over time. These findings may better inform COVID-19 identification in high-immunity settings and demonstrate additional benefits of vaccination.

The spike glycoprotein is a key factor in the infection cycle of SARS-CoV-2, as it mediates both receptor recognition and membrane fusion by the virus. Therefore, in this study, we aimed to design a multi-peptide conjugate vaccine against SARS-CoV-2, targeting the early stages of the virus's life cycle. We used iBoost technology, which is designed to induce immune responses against low- or non-immunogenic epitopes. We selected six peptide sequences, each representing a key domain of the spike protein (i.e., receptor binding domain (RBM), subdomain 1 (SD1), subdomain 2 (SD2), S1/S2, fusion peptide and the S2' sequences (FP + S2'), heptad repeat 1 (HR1)). Immunization studies in mice displayed targeted humoral and cellular immune responses against specific peptides of the spike protein simultaneously, while inducing cross-protection against the Delta and Omicron coronavirus variants. Moreover, vaccinated hamsters challenged with SARS-CoV-2 elicited high antibody levels against key peptides, induced early neutralizing antibody responses and resulted in less weight loss compared to controls. This highlights the potential for improving viral control and disease outcomes when utilizing this strategy. Therefore, by using iBoost technology in conjunction with our peptide design strategy, we were able to successfully target non-immunodominant regions in the spike protein while activating both arms of the adaptive immune system.

Although, COVID-19 has resulted in over 7 million deaths globally, many questions still remain about the risk factors for disease severity and the effects of variants and vaccinations over the course of the pandemic. To address this gap, we conducted a retrospective analysis of electronic health records from COVID-19 patients over 2.5 years of the COVID-19 pandemic to identify associated clinical features.

We analyze a retrospective cohort of 21,312 acute-care patients over a 2.5 year period and define six clinical trajectory groups (TGs) associated with demographics, diagnoses, vitals, labs, imaging, consultations, and medications.

We show that the proportion of mild patients increased over time, particularly during Omicron waves. Additionally, while mild and fatal patients had differences in age, age did not distinguish patients with severe versus critical disease. Furthermore, we find that both male sex and Hispanic/Latino ethnicity are associated with more severe/critical TGs. More severe patients also have a higher rate of neuropsychiatric diagnoses and consultations, along with an immunological signature of high neutrophils and immature granulocytes, and low lymphocytes and monocytes. Interestingly, low albumin is one of the best lab predictors of COVID-19 severity in association with higher malnutrition in severe/critical patients, raising concern of nutritional insufficiency influencing COVID-19 outcomes. Despite this, only a small fraction of severe/critical patients had nutritional labs checked (e.g. Vitamin D, thiamine, B vitamins) or received vitamin supplementation.

Our findings expand on clinical risk factors in COVID-19, and highlight the interaction between severity, nutritional status, and neuropsychiatric complications in acute care patients to enable identification of patients at risk for severe disease.

Although COVID-19 is no longer a global public health threat, its consequences persist, with long COVID affecting at least 10% of patients and manifesting in various organ systems. National and international health agencies promoted vaccination to enhance population immunity, prioritizing healthcare personnel due to their high occupational risk. In a previous study, we found that the risk of SARS-CoV-2 transmission among dental teams in Germany was not higher than in the general population. This follow-up investigation aims to assess the vaccination status and the prevalence and severity of long COVID symptoms among dental teams in Germany. As part of a follow-up investigation involving the original cohort, 267 team members from 186 German dental practices previously included in the initial study completed an online questionnaire. The questionnaire covered three topics: (1) vaccination status, (2) confirmed COVID-19 diagnosis, and (3) self-reported long COVID symptoms. One hundred and seventy-two dentists (64.4%), 74 dental assistants (27.7%) and 21 dental hygienists (7.9%) completed the questionnaire. In total, 245 participants (91.8%) were at least once vaccinated. A COVID-19 infection after January 1st 2021 was reported by 146 (54.7%) participants, of which 33 participants (22.6%) suffered from long COVID symptoms. Our results showed lower vaccination rates among dental auxiliary personnel compared to dentists (95.9% vs. 84.2%). Individuals with long COVID symptoms were more often dental assistants (48.5% vs. 29.2%) or dental hygienists (15.2% vs. 8.0%) than dentists (36.4% vs. 62.8%) compared to the group not reporting long COVID symptoms (p = 0.025). In addition, it is unlikely that dental healthcare personnel are more prone to experiencing more severe symptoms compared to the general population. Vaccination against SARS-CoV-2 is likely to help against symptoms of long COVID.

The spike protein (SP) is an outward-projecting transmembrane glycoprotein on viral surfaces. SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), responsible for COVID-19 (Coronavirus Disease 2019), uses SP to infect cells that express angiotensin converting enzyme 2 (ACE2) on their membrane. Remarkably, SP has the ability to cross the blood-brain barrier (BBB) into the brain and cause cerebral damage through various pathomechanisms. To combat the COVID-19 pandemic, novel gene-based products have been used worldwide to induce human body cells to produce SP to stimulate the immune system. This artificial SP also has a harmful effect on the human nervous system.

Narrative review.

This narrative review presents the crucial role of SP in neurological complaints after SARS-CoV-2 infection, but also of SP derived from novel gene-based anti-SARS-CoV-2 products (ASP).

Literature searches using broad terms such as "SARS-CoV-2", "spike protein", "COVID-19", "COVID-19 pandemic", "vaccines", "COVID-19 vaccines", "post-vaccination syndrome", "post-COVID-19 vaccination syndrome" and "proteinopathy" were performed using PubMed. Google Scholar was used to search for topic-specific full-text keywords.

The toxic properties of SP presented in this review provide a good explanation for many of the neurological symptoms following SARS-CoV-2 infection and after injection of SP-producing ASP. Both SP entities (from infection and injection) interfere, among others, with ACE2 and act on different cells, tissues and organs. Both SPs are able to cross the BBB and can trigger acute and chronic neurological complaints. Such SP-associated pathologies (spikeopathies) are further neurological proteinopathies with thrombogenic, neurotoxic, neuroinflammatory and neurodegenerative potential for the human nervous system, particularly the central nervous system. The potential neurotoxicity of SP from ASP needs to be critically examined, as ASPs have been administered to millions of people worldwide.

Pulmonary delivery of bioactives has shown to be a promising route for the treatment of respiratory conditions, however, numerous physiological barriers, such as mucociliary clearance and immune responses, pose significant hurdles to treatment efficacy. These barriers specifically affect labile bioactives such as mRNA, peptides, proteins, and probiotics, which are susceptible to degradation due to the prevailing conditions. Various drug delivery platforms have been developed to address these challenges, including, among others, polymeric nanoparticles, micelles, liposomes, and solid lipid nanoparticles that encapsulate and protect the labile bioactives during formulation and administration, enabling improved bioavailability, sustained release, and enhanced formulation stability, while further modification of these platforms allows for targeted drug delivery. This review explores the advanced drug delivery systems that have been designed to protect and release labile active agents in a controlled and targeted manner to the lung, with a specific focus provided on the physiological barriers to effective pulmonary delivery and the formulation considerations to overcome these challenges. The outlook of this pertinent field of study has additionally been provided, highlighting the significant potential of the pulmonary delivery of labile bioactive agents for the prevention and treatment of a variety of respiratory ailments.

While SARS-CoV-2 vaccines have shown strong efficacy, the continued emergence of new viral variants raises concerns about the ongoing and future public health impact of COVID-19, especially in locations with suboptimal vaccination uptake. We investigated viral and host factors, including vaccination status, that were associated with SARS-CoV-2 disease severity in a setting with low vaccination rates. We analyzed clinical and demographic data from 1,957 individuals in the state of Georgia, USA, coupled with viral genome sequencing from 1,185 samples. We found no specific mutations associated with disease severity. Compared to those who were unvaccinated, vaccinated individuals experienced less severe SARS-CoV-2 disease, and the effect was similar for both variants. Vaccination within the prior 3-9 months was associated with decreased odds of moderate disease, severe disease, and death. Older age and underlying health conditions, especially immunosuppression and renal disease, were associated with increased disease severity. Overall, this study provides insights into the impact of vaccination status, variants/mutations, and clinical factors on disease severity in SARS-CoV-2 infection when vaccination rates are low. Understanding these associations will help refine and reinforce messaging around the crucial importance of vaccination in mitigating the severity of SARS-CoV-2 disease.

Kidney transplant recipients (KTRs) are at risk of coronavirus disease 2019 (COVID-19) complications and mortality. This study examined factors associated with moderate, severe, or critical COVID-19 infection among KTRs during the Omicron-predominant period.

This single-center retrospective study included KTRs aged ≥18 years diagnosed with COVID-19 between January 1, 2022, and December 31, 2023. Mild infection was defined as symptomatic illness without lower respiratory tract infection (LRTI); moderate infection as LRTI without hypoxia; severe infection as oxygen saturation <94% on room air; and critical infection as respiratory failure, septic shock, or multiple organ dysfunction. We compared the characteristics of KTRs with asymptomatic or mild COVID-19 versus those with moderate to critical disease. Logistic regression analysis was performed to identify factors associated with moderate to critical illness.

Most KTRs (94.4%) had received three or more vaccine doses. Of 603 episodes of COVID-19 infection during the study period, 554 (91.9%) were asymptomatic or mild, while 49 (8.1%) were moderate to critical. Multivariate analysis revealed that older age (adjusted odds ratio [aOR], 1.037; 95% confidence interval [CI], 1.006-1.069) and longer symptom duration before seeking care (aOR, 1.288; 95% CI, 1.155-1.436) were associated with higher odds of moderate to critical disease. Protective factors included receiving a vaccine booster within the past year (aOR, 0.414; 95% CI, 0.212-0.809) and higher glomerular filtration rate (aOR, 0.971; 95% CI, 0.956-0.986).

KTRs should seek care early if infected with COVID-19 and keep their COVID-19 vaccine boosters updated within 1 year of the last dose.

We modeled the impact of initiating one-dose influenza vaccination at 3 months vs 6 months after declaration of a pandemic over a 1-year timeframe in the US population. Three vaccine effectiveness (VE) and two pandemic severity levels were considered, using an epidemic curve based on typical seasonal influenza epidemics. Vaccination from 3 months with a high, moderate, or low effectiveness vaccine would prevent ~95%, 84%, or 38% deaths post-vaccination, respectively, compared with 21%, 18%, and 8%, respectively following vaccination at 6 months, irrespective of pandemic severity. While the pandemic curve would not be flattened from vaccination from 6 months, a moderate/high effectiveness vaccine could flatten the curve if administered from 3 months. Overall, speed of initiating a vaccination campaign is more important than VE in reducing the health impacts of an influenza pandemic. Preparedness strategies may be able to minimize future pandemic impacts by prioritizing rapid vaccine roll-out.

Background: The rapid genetic evolution of SARS-CoV-2 has led to the emergence of immune-evading, highly transmissible variants of concern (VOCs). This prompts the need for next-generation vaccines that elicit robust mucosal immunity in the airways to directly curb viral infection. Objective: Here, we investigate the impact of heterologous variant prime-boost regimens on humoral responses, focusing on intramuscular (IM) and intranasal (IN) routes of administration. Using a murine model, we assessed the immunogenicity of unadjuvanted protein boosts with Wu-1, Omicron BA.4/5, or Wu-1 + BA.4/5 spike antigens following monovalent or bivalent IM priming with mRNA-LNP vaccines. Results: IM priming induced strong systemic total and neutralizing antibody responses that were further enhanced by IN boosts with BA.4/5. IN boosting achieved the broadest serum neutralization across all VOCs tested. Notably, bivalent mRNA-LNP IM priming induced robust, cross-variant serum neutralizing antibody production, independent of subsequent IN boost combinations. Conclusions: Our findings highlight the benefit of including distinct antigenic variants in the prime vaccination followed by a variant-tailored IN boost to elicit both systemic and mucosal variant-specific responses that are potentially capable of reducing SARS-CoV-2 transmission.

The accelerated development of vaccines to mitigate COVID-19 was crucial in the response to the 2020 pandemic. The success of vaccination strategies relies upon adequate uptake across the population. In the United Kingdom, COVID-19 vaccination began in December 2020, with population groups invited in priority groups according to age and clinical vulnerability. By February 2021, uptake rates were lower in North West London than the national average. This study aimed to explore whether behaviourally-informed (BI) letters could increase the rate of first vaccine uptake in previously uncontactable residents. BI letters were designed to invoke a sense of ownership, and highlight the ease of accessing a vaccine. Letters were sent to unvaccinated uncontactable residents in a Central London Borough over a 3-week period. Three neighbouring boroughs in London with similar non-responder data acted as controls. A linear difference in difference (DID) analysis assessed the change in the rate of vaccine uptake across all four boroughs, with percentage point change adjusted for covariates including ethnicity, age, gender and socioeconomic status. In total, 10,161 residents in Central London were eligible to receive our BI letter. All four boroughs demonstrated an increase in vaccination, with an absolute increase of 4.3 % in the intervention borough. Our linear DID analysis showed a 14.7 % increase in vaccination likelihood in the intervention borough following the intervention on average across all weeks included in the study. Residents with a mixed or multiple ethnic background were less likely to receive a COVID-19 vaccination. Those from a more deprived socioeconomic background demonstrated the largest rate of change. Our study highlights the effectiveness of traditional communication strategies such as letters in those who are uncontactable by other means. Incorporating behavioural science principles into healthcare communication, such as those designed to evoke a sense of ownership can enhance their effectiveness.

The Omicron BA.2.86 subvariants, JN.1, KP.2, and KP.3, have become predominant globally, raising concerns about their immune evasion from vaccines and monoclonal antibody (mAb) treatments. These variants harbor more receptor-binding domain (RBD) mutations than the XBB and EG.5 sub-lineages, which are already known to compromise vaccine and therapeutic efficacy. We evaluated sera from individuals vaccinated with inactivated vaccines, with or without breakthrough infections, as well as COVID-19 convalescents. Our results showed a substantial decrease in serum neutralizing activity against the JN.1, KP.2, XBB.1.5, and EG.5.1 variants compared to BA.2. Additionally, we developed 19 neutralizing antibodies from memory B cells, with some retaining efficacy against earlier Omicron variants. However, potency was notably diminished against newer subvariants like BF.7, BQ.1, XBB.1.5, and BA.2.86. Of mAbs, those isolated from COVID-19 convalescents, particularly SA-3, exhibited exceptional potency across ten variants from BA.2 to KP.2, with IC50 values ranging from 0.006 to 2.546 μg/mL. However, SA-3 had lost neutralizing activity against the KP.3 due to the Q493E mutation, but the KP.3 became susceptible to neutralization by the other mAb, SA-6. In contrast, SA-6 was unable to neutralize KP.2 because of the presence of R346T mutation. Our findings underscore the importance of continuous surveillance of viral evolution and the need for updated vaccines and therapeutics to combat the ongoing evolution of SARS-CoV-2, particularly in the context of emerging variants that escape both vaccine-induced immunity and monoclonal antibody treatments.

Understanding similarities and differences between hesitancy for influenza and COVID-19 vaccines could facilitate strategies to improve public receptivity toward vaccination.

We compared hesitancy for COVID-19 vaccines during the first 13 months of availability (January 2021-January 2022) with hesitancy for influenza vaccines in the 15 months prior to COVID-19 vaccine availability (October 2019-December 2020) among adults hospitalized with acute respiratory illness at 21 hospitals in the United States. We interviewed patients regarding vaccination status, willingness to be vaccinated, and perceptions of vaccine safety and efficacy. We used multivariate logistic regression to identify factors associated with vaccine hesitancy.

Among 12,292 patients enrolled during the COVID-19 vaccine period, 5485 (44.6 %) were unvaccinated. Patient characteristics associated with not receiving the COVID-19 vaccine included younger age, female sex, higher BMI, lack of health insurance, absence of chronic comorbid medical conditions, no or rare influenza vaccination in prior years, higher CDC social vulnerability index (SVI), a measure of external stresses that may negatively impact health, living in the Midwest or southern US, lack of college or higher education, and not wearing a mask. Among 983 patients enrolled during the influenza vaccination period, 381(37.8 %) were unvaccinated. Characteristics associated with not receiving the influenza vaccine included no or one chronic comorbid medical condition, no or rare influenza vaccination in prior years, being a current smoker, and higher SVI. Discussion with healthcare providers was a reason for vaccination for 27.7 % (167) for influenza and 8.3 % (564) for COVID-19 and to decline vaccination for 0.5 % Ten great public health achievements-United States (2011) (2) for influenza and 2.2 % (118) for COVID-19.

We found that higher SVI scores and lack of prior influenza vaccination were associated with hesitancy for both COVID-19 and influenza vaccines. There were regional variations in COVID-19 vaccine acceptance and discussions with HCPs significantly influenced acceptance for both vaccines.

The length of hospital stays for severe COVID-19 cases significantly impacts the overall burden on the health system. Current COVID-19 vaccines have proven effective at reducing severe cases. However, the influence of vaccination status on the progression of COVID-19 after hospitalization is not well understood. Here, we estimated the impact of vaccination on the length of stay of hospitalized COVID-19 cases in Brazil.

We utilized nationwide data from hospital stays due to COVID-19 and the vaccination status of over 1.6 million individuals who tested positive for COVID-19 between January 17, 2021, and January 31, 2022. A competing-risk survival analysis was conducted to assess the COVID-19 in-hospital progression. We considered the hospital pathway according to four states: ward, ICU, discharge and death and measuring the length of stay accordingly.

Over half of hospital patients were unvaccinated. For patients aged 50-69-year-olds, the average length of stay for those discharged directly from the hospital ward (ward-to-discharge) ranged from 12.51 days (95 % CI, 12.39-12.63) in the unvaccinated to 11.02 days (95 % CI, 10.98-11.07) in booster recipients. Similar results were observed in the 20-49 and 70 or + age groups. For all age groups, the average time between hospital admission and ICU entrance was shorter in the unvaccinated. In the 50-69 age group, the average interval between ICU and discharge was 19.29 days (95 % CI, 18.95-19.64) in the unvaccinated and 16.92 days (95 % CI, 16.78-17.07) in the booster recipients, with a similar trend in other age groups. A higher discharge probability was observed among vaccinated individuals including hospital-to-discharge and ICU-to-discharge pathways.

Vaccination reduced hospital admissions and length-of-stay across the hospital-to-discharge and ICU-to-discharge pathways, contributing to a reduced health system burden. Our results demonstrate that even when vaccines do not prevent severe cases leading to hospitalizations, they significantly shorten the duration of hospital stays.

Fundação Oswaldo Cruz (FIOCRUZ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), Pan American Health Organization (PAHO), Departamento de Ciência e Tecnologia da Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde do Ministério da Saúde do Brasil (DECIT/SCTIE/MS).

This study investigated post-coronavirus disease 2019 (COVID-19) sequelae among a sample of the Chinese population, and determined the statistical significance of correlations between age, sex, number of COVID-19 vaccinations, number of SARS-CoV-2 infections, development of pneumonia, use of specific drugs (namatevir/ritonavir, azvudine, molnupiravir), chronic underlying diseases, and post-COVID-19 sequelae.

Data from 869 patients, who visited the Emergency Department of Beijing Shijitan Hospital (Beijing, China) between December 7, 2022 to January 31, 2024, were collected. The criteria for admission: Age ≥ 14 years old, and diagnosed with ≥ 1 positive result on nucleic acid or antigen tests. Retrospectively analyzed the main manifestations of sequelae, statistical analysis of the relationship between age; sex; underlying diseases; number of COVID-19 vaccinations received; use of specific antiviral drugs for COVID-19 and prognosis, and statistical analyses, including logistic regression, were performed. Differences with P < 0.05 were considered to be statistically significant. Before entering the model, variables are screened using stepwise regression to ensure that the selected variables are the main ones related to the research question, thereby controlling for confounding factors. SPSS version 27 (IBM Corp. Armonk, NY, USA) was used for statistical analysis. In this study, the duration of sequelae ranged from 2 to 13 months.

This study retrospectively analyzed 869 patients (415 male, 454 female), with an average age of 61.52 ± 23.09 years. There were 401 patients without underlying conditions and 468 patients with one or more underlying conditions. Regarding COVID-19 vaccination status, 320 patients were unvaccinated, while 576 patients received at least one dose of the COVID-19 vaccine. Additionally, 514 patients received antiviral medication, while 355 did not receive antiviral treatment. The primary manifestations of post-COVID-19 included shortness of breath, dizziness and weakness, chronic pneumonia, asthma, and reduced sense of smell. Individuals ≥ 70 years of age were more prone to COVID-19 pneumonia. Patients with underlying disease(s) exhibited statistically higher mortality rates after diagnosis of COVID-19. Vaccination against COVID-19 and the use of specific drugs had a statistically significant effect on mortality and the occurrence of post-COVID-19 sequelae. There was no statistically significant difference in COVID-19 infection rates between males and females, although males were more prone to COVID-19 pneumonia. Young women with COVID-19 often experienced no sequelae, and elderly males exhibited a high mortality rate.

COVID-19 booster vaccinations mitigate transmission and reduce the morbidity and mortality associated with infection. However, the optimal date for booster administration remains uncertain. Geographic variation in infection rates throughout the year makes it challenging to intuit the best yearly booster administration date to effectively prevent infection, and also challenging to provide best guidance on how to alter booster administration in response to a breakthrough infection.

We leveraged longitudinal antibody and reinfection probabilities with spatiotemporal projections of COVID-19 incidence to develop a geographically informed approach to optimizing the timing of booster vaccination. We assessed the delay in booster vaccination that is warranted following breakthrough infections whenever they occur during the year, enabling a personalized assessment of optimal timing that acknowledges and respects diversity of COVID-19 immune status, addressing a substantial barrier to uptake.

Yearly booster vaccination on any date is beneficial to prevention of infection. However, each location exhibits as much as a 3-4-fold range in degree of protection by date of uptake. Optimal COVID-19 booster vaccination dates are location-specific, typically in early autumn in the Northern Hemisphere. Infection late in the interval between boosts substantially alters the optimal boosting date.

Considerable benefit accrues from aptly timing COVID-19 booster vaccination campaigns, which can be tailored to specific locations. Individuals can acquire the greatest benefit from booster vaccination by timing it optimally, including delaying in cases of infection late in the interval between boosts. These results provide location-specific guidance for public health policy, healthcare provider recommendations, and individual decision-making.

Coronavirus disease 2019 (COVID-19) is a strong risk factor for venous thromboembolism (VTE). Few studies have evaluated the effectiveness of COVID-19 vaccination in preventing hospitalization for COVID-19 with VTE.

Adults hospitalized at 21 sites between March 2021 and October 2022 with symptoms of acute respiratory illness were assessed for COVID-19, completion of the original monovalent messenger RNA (mRNA) COVID-19 vaccination series, and VTE. Prevalence of VTE was compared between unvaccinated and vaccinated patients with COVID-19. The vaccine effectiveness (VE) in preventing COVID-19 hospitalization with VTE was calculated using a test-negative design. The VE was also stratified by predominant circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant.

Among 18 811 patients (median age [interquartile range], 63 [50-73] years; 49% women; 59% non-Hispanic white, 20% non-Hispanic black, and 14% Hispanic; and median of 2 comorbid conditions [interquartile range, 1-3]), 9792 were admitted with COVID-19 (44% vaccinated), and 9019 were test-negative controls (73% vaccinated). Among patients with COVID-19, 601 had VTE diagnosed by hospital day 28, of whom 170 were vaccinated. VTE was more common among unvaccinated than vaccinated patients with COVID-19 (7.8% vs 4.0%; P = .001). The VE against COVID-19 hospitalization with VTE was 84% overall (95% confidence interval, 80%-87%), and VE stratified by predominant circulating variant was 88% (73%-95%) for Alpha, 93% (90%-95%) for Delta, and 68% (58%-76%) for Omicron variants.

Vaccination with the original monovalent mRNA series was associated with a decrease in COVID-19 hospitalization with VTE, though data detailing prior history of VTE and use of anticoagulation were not available. These findings will inform risk-benefit considerations for those considering vaccination.

To provide globally representative data on hospitalization and death in recently SARS-CoV-2-positive ambulatory populations.

We enrolled SARS-CoV-2-positive ambulatory adults in the cohort studies, ICOS (47 sites, 5 continents), and PCOS (Liberia) and followed for 28-days. Kaplan-Meier estimates of percentage of those hospitalized or died were derived. Risk factors for hospitalization, death, and failure to recover were identified using Cox and logistic models respectively.

9817(ICOS) and 125(PCOS) participants, 46.7% male; median age 43 years; 24.5% with comorbidity(s); 0.8% pregnant; 9.3% SARS-CoV-2 vaccinated, were enrolled June-2020 and January-2022. By 28 days, 424(4.3%) participants were hospitalized or had died; most within 7 days of enrolment(3.4%). Hospitalization or death declined over calendar time i.e. 7.5%(2020); 4.1(first-half 2021) and 2.1%(second-half 2021), P < 0.0001. Older age, male sex, comorbidities, pregnancy, symptomatic disease were each independently associated with hospitalization or death; SARS-CoV-2 vaccination reduced this risk. At 28 days, 26.1% and 29.9% reported ongoing symptoms and failure to return to pre-morbid health respectively.

These global SARS-CoV-2 ambulatory cohort studies identified demographic/clinical risks for hospitalization or death. Vaccination does not fully explain hospitalization and death declines over time. Symptomatic recovery and return to premorbid health were incomplete at 28 days in ≈one third.

The first vaccines approved against SARS-CoV-2, mRNA-1273 and BNT162b2, utilized mRNA platforms. However, little is known about the proteomic markers and pathways associated with host immune responses to mRNA vaccination. In this proof-of-concept study, sera from male and female vaccine recipients were evaluated for proteomic and immunologic responses 1-month and 6-months following homologous third vaccination.

An aptamer-based (7,289 marker) proteomic assay coupled with traditional serology was leveraged to generate a comprehensive evaluation of systemic responsiveness in 64 and 68 healthy recipients of mRNA-1273 and BNT162b2 vaccines, respectively.

Sera from female recipients of mRNA-1273 showed upregulated indicators of inflammatory and immunological responses at 1-month post-third vaccination, and sera from female recipients of BNT162b2 demonstrated upregulated negative regulators of RNA sensors at 1-month. Sera from male recipients of mRNA-1273 showed no significant upregulation of pathways at 1-month post-third vaccination, though there were multiple significantly upregulated proteomic markers. Sera from male recipients of BNT162b2 demonstrated upregulated markers of immune response to doublestranded RNA and cell-cycle G(2)/M transition at 1-month. Random Forest analysis of proteomic data from pre-third-dose sera identified 85 markers used to develop a model predictive of robust or weaker IgG responses and antibody levels to SARS-CoV-2 spike protein at 6-months following boost; no specific markers were individually predictive of 6-month IgG response. Thirty markers that contributed most to the model were associated with complement cascade and activation; IL-17, TNFR pro-apoptotic, and PI3K signaling; and cell cycle progression.

These results demonstrate the utility of proteomics to evaluate correlates or predictors of serological responses to SARS-CoV-2 vaccination.

Coronavirus disease (COVID-19) quickly spread around the world after its initial identification in Wuhan, China in 2019 and became a global public health crisis. COVID-19 related hospitalizations and deaths as important disease outcomes have been investigated by many studies while less attention has been given to the relationship between these two outcomes at a public health unit level. In this study, we aim to establish the relationship of counts of deaths and hospitalizations caused by COVID-19 over time across 34 public health units in Ontario, Canada, taking demographic, geographic, socio-economic, and vaccination variables into account.

We analyzed daily data of the 34 health units in Ontario between March 1, 2020 and June 30, 2022. Associations between numbers of COVID-19 related deaths and hospitalizations were explored over three subperiods according to the availability of vaccines and the dominance of the Omicron variant in Ontario. A generalized additive model (GAM) was fit in each subperiod. Heterogeneity across public health units was formulated via a random intercept in each of the models.

Mean daily COVID-19 deaths increased quickly as daily hospitalizations increased, particularly when daily hospitalizations were less than 20. In all the subperiods, mean daily deaths of a public health unit was significantly associated with its population size and the proportion of confirmed cases in subjects over 60 years old. The proportion of fully vaccinated (2 doses of primary series) people in the 60 + age group was a significant factor after the availability of the COVID-19 vaccines. The deprivation index, a measure of poverty, had a significantly positive effect on COVID-19 mortality after the dominance of the Omicron variant in Ontario. Quantification of these effects was provided, including effects related to public health units.

The differences in COVID-19 mortality across health units decreased over time, after adjustment for other covariates. In the last subperiod when most public health protections were released and the Omicron variant dominated, the least advantaged group might suffer higher COVID-19 mortality. Interventions such as paid sick days and cleaner indoor air should be made available to counter lifting of health protections.

As older age and having certain comorbidities can influence humoral responses to vaccination, we studied antibody responses after the COVID-19 booster campaigns in nursing home (NH) residents.

In a two year longitudinal study with Dutch NH residents (n = 107), aged 50 years and over, we monitored antibody responses in serum prior to and after vaccination with a third, fourth BNT162b2 (wild-type; WT), and a BNT162b2 bivalent (WT/OMI BA.1) fifth vaccine. Data on vaccinations, infections, comorbidities, and, for some participants, clinical symptoms after infection were obtained with questionnaires. Data were compared to antibody responses of BNT162b2-vaccinated, healthier community-dwelling older adults (n = 32) from the general population.

The booster vaccinations substantially increased anti-WT and anti-Omicron SARS-CoV-2 Spike S1 (S1) and Spike protein receptor binding domain (RBD)-antibody concentrations of NH residents. This resulted in comparable antibody levels between NH residents and healthier community-dwelling older adults and between infection-naïve and infected NH residents, and in a decline in treatment duration and clinical symptom severity in SARS-CoV-2-infected NH residents. Between one and twelve months after the bivalent fifth dose, anti-Omicron BA.1 antibody levels of the NH residents waned faster than those against the WT strain.

The booster vaccinations upheld humoral responses of NH residents to WT and Omicron SARS-CoV-2. This, in addition to the less virulent circulating strains, decreased symptom severity and treatment durations for SARS-CoV-2-infected NH residents. Boosting this vulnerable group should, therefore, be continued to prevent waning of humoral immunity and achieve sufficient protection especially against newly emerging variants of concern.

Coronavirus disease 2019 (COVID-19) was extraordinarily harmful, with high rates of infection and hospitalization. This study aimed to evaluate the impact of COVID-19 vaccination status and other factors on hospitalization and disease severity, using data from Nagasaki Prefecture, Japan. Confirmed cases of COVID-19 infection with vaccination status were included and the differences in characteristics between different vaccination statuses, hospitalization or not, and patients with varying levels of disease severity were analyzed. Furthermore, logistic regression was used to calculate odds ratio (ORs) and 95% confidence intervals (CI) to evaluate the association of various factors with hospitalization and disease severity. From March 14, 2020 to August 31, 2022, 23,139 patients were unvaccinated 13,668 vaccinated the primary program with one or two doses, and 4,575 completed the booster. Vaccination reduced the risk of hospitalization with an odd ratio of 0.759 (95% CI: 0.654-0.881) and the protective effect of completed booster vaccination was more pronounced (OR: 0.261, 95% CI: 0.207-0.328). Similarly, vaccination significantly reduced the risk of disease severity (vaccinated primary program: OR: 0.191, 95% CI: 0.160-0.228; completed booster vaccination: OR: 0.129, 95% CI: 0.099-0.169). Overall, unvaccinated, male, elderly, immunocompromised, obese, and patients with other severe illness factors were all risk factors for COVID-19-related hospitalization and disease severity. Vaccination was associated with a decreased risk of hospitalization and disease severity, and highlighted the benefits of completing booster.

This study aimed to explore the clinical profile and the impact of vaccination status on various health outcomes among COVID-19 patients diagnosed in different phases of the pandemic, during which several variants of concern (VOCs) circulated in South Carolina (SC). The current study included 861,526 adult COVID-19 patients diagnosed between January 2021 and April 2022. We extracted their information about demographic characteristics, vaccination, and clinical outcomes from a statewide electronic health record database. Multiple logistic regression models were used to compare clinical outcomes by vaccination status in different pandemic phases, accounting for key covariates (e.g. historical comorbidities). A reduction in mortality was observed among COVID-19 patients during the whole study period, although there were fluctuations during the Delta and Omicron dominant periods. Compared to non-vaccinated patients, full-vaccinated COVID-19 patients had lower mortality in all dominant variants, including Pre-alpha (adjusted odds ratio [aOR]: 0.33; 95%CI: 0.15-0.72), Alpha (aOR: 0.58; 95%CI: 0.42-0.82), Delta (aOR: 0.28; 95%CI: 0.25-0.31), and Omicron (aOR: 0.29; 95%CI: 0.26-0.33) phases. Regarding hospitalization, full-vaccinated parties showed lower risk of hospitalization than non-vaccinated patients in Delta (aOR: 0.44; 95%CI: 0.41-0.47) and Omicron (aOR: 0.53; 95%CI: 0.50-0.57) dominant periods. The findings demonstrated the protection effect of the COVID-19 vaccines against all VOCs, although some of the full-vaccinated population still have symptoms to varying degrees from COVID-19 disease at different phases of the pandemic.

Coronavirus disease 2019 (COVID-19) pneumonia requires considerable healthcare resources.

Examine if a single dose of infliximab or abatacept, in addition to remdesivir and steroids, decreased resource utilization among participants hospitalized with COVID-19 pneumonia.

Accelerating COVID-19 Therapeutic Interventions and Vaccines Immunomodulator (ACTIV-1 IM) master protocol was a randomized, placebo-controlled trial examining the potential benefit in time to recovery and mortality of immunomodulators infliximab, abatacept, and cenicriviroc. This observational study performs a secondary analysis of the infliximab, abatacept, and common placebo participants to examine resource utilization. Hospital days, intensive care unit days, days with supplemental oxygen, days with high flow nasal cannula or non-invasive ventilation, ventilator days, and days of extracorporeal membrane oxygenation were each examined. Proportional odds models were used to compare days alive and free of resource use over 28 days between infliximab and placebo groups and between abatacept and placebo groups.

Infliximab infusion, compared to placebo, was associated with greater odds of being alive and free of all interventions tested. Abatacept use was associated only with greater odds of days alive and free of hospitalization and supplemental oxygen.

Infliximab and abatacept use were associated with decreased use of healthcare resources over 28 days compared to placebo, but the absolute differences were small.

www.clinicaltrials.gov (NCT04593940).

SARS-CoV-2 is continually evolving with new variants to evade protective immunity and cause new infections. This study aimed to assess infection-acquired immunity and hybrid immunity against re-infection or severe COVID-19.

During 2020-2023, we collected 890 serum samples from individuals infected with SARS-CoV-2 variants including wild type, D614G, Alpha, Delta, BA.1, BA.2, BA.2.76, BA.5.2, BF.7, XBB, and EG.5. The levels of serum neutralizing antibodies (NAbs) against 18 diverse SARS-CoV-2 variants were determined using a bead-based high-throughput broad neutralizing-antibody assay.

In the initial wave of the COVID-19 pandemic, >75% of the patients demonstrated robust NAb responses against the ancestral SARS-CoV-2, during a period when vaccines were not yet available. After the emergence of the Omicron variant, the seroprevalence of anti-Omicron NAbs among the patients increased rapidly. By April 2023, when XBB variant was predominant, approximately 80% of the patients demonstrated >50% neutralization against the highly immune-evasive XBB lineages. Three serotypes of SARS-CoV-2, namely non-Omicron, Omicron, and XBB serotypes, were identified, with the strong likelihood of further changes occurring as the virus mutating. Generally, NAbs elicited by a previous serotype could not typically effectively protect against another serotype that emerges later in the evolutionary stages.

Our results firstly demonstrated the synergistic evolution between host immunity and SARS-CoV-2 variants in the real world, which would be helpful to develop future vaccines and public health strategies.