Clostridium tertium Bacteremia: A Marker of an Underlying Perforated Colonic Diverticular Disease in a Non-Neutropenic Patient With COVID-19.

Clostridium tertium (C. tertium) is an aero-tolerant, gram-positive, endospore-forming, and non-exotoxin-producing bacillus that has colonized the gastrointestinal tract of animals and humans. It is considered a rare pathogen of humans, possibly because of its low virulence. Most C. tertium infections in the reviewed literatures were predominately reported among neutropenic hosts with hematological malignancies. A 66-year-old female patient with a past medical history of type II diabetes mellitus and chronic obstructive pulmonary disease was admitted with coronavirus disease 2019 (COVID-19) that initially required non-invasive ventilation. The patient developed septic shock due to C. tertium bacteremia. Computed tomography of the abdomen depicted free intraperitoneal gas and sigmoid colon perforation. Exploratory laparotomy revealed perforated sigmoid diverticulitis, and Hartmann's procedure was performed. The patient received a prolonged course of susceptibility-guided antibiotics to clear C. tertium bacteremia. The authors described a rare case of C. tertium bacteremia as a marker of underlying perforated colonic diverticulitis in a non-neutropenic patient with COVID-19 that necessitated operative procedure intervention for primary source control and an extended course of targeted antibiotic therapy to treat the Clostridial infection. Our case reaffirmed the available literature that suggested the presence of C. tertium bacteremia in non-neutropenic patients raises suspicion of an associated gastrointestinal tract pathology that should warrant a diagnostic workup to identify the infection source culprit.

Cardiac Arrest With Spontaneous Coronary Artery Dissection in a Young Female.

Spontaneous coronary artery dissection (SCAD) is a rare condition that has variable clinical presentations requiring a very high index of suspicion for diagnosis. We present here a case of a young female with SCAD who initially presented with chest pain and syncope, with progression to cardiac arrest.

Antibodies to Crucial Epitopes on HSV-2 Glycoprotein D as a Guide to Dosing an mRNA Genital Herpes Vaccine.

The toxicity of mRNA-lipid nanoparticle (LNP) vaccines depends on the total mRNA-LNP dose. We established that the maximum tolerated dose of our trivalent mRNA-LNP genital herpes vaccine was 10 µg/immunization in mice. We then evaluated one of the mRNAs, gD2 mRNA-LNP, to determine how much of the 10 µg total dose to assign to this immunogen. We immunized mice with 0.3, 1.0, 3.0, or 10 µg of gD2 mRNA-LNP and measured serum IgG ELISA, neutralizing antibodies, and antibodies to six crucial gD2 epitopes involved in virus entry and spread. Antibodies to crucial gD2 epitopes peaked at 1 µg, while ELISA and neutralizing titers continued to increase at higher doses. The epitope results suggested no immunologic benefit above 1 µg of gD2 mRNA-LNP, while ELISA and neutralizing titers indicated higher doses may be useful. We challenged the gD2 mRNA-immunized mice intravaginally with HSV-2. The 1-µg dose provided total protection, confirming the epitope studies, and supported assigning less than one-third of the trivalent vaccine maximum dose of 10 µg to gD2 mRNA-LNP. Epitope mapping as performed in mice can also be accomplished in phase 1 human trials to help select the optimum dose of each immunogen in a multivalent vaccine.

Clinical characteristics and outcomes of the first two waves of the COVID-19 pandemic in a community hospital: a retrospective cohort study.

Objective: To describe the clinical characteristics and outcomes of two waves of the COVID-19 pandemic. Methods: A de-identified dataset of patients with COVID-19 admitted to our community hospital in Evanston, Illinois, from March 1, 2020 to February 28, 2021 was retrospectively reviewed. Patients from the first wave were identified as those admitted during the initial peak of admissions observed at our hospital between March 1, 2020 and September 3, 2020. The second wave was defined as those admitted during the second peak of admissions observed between October 1, 2020 and February 28, 2021. Results: In total, 671 patients were included. Of these, 399 (59.46%) were identified as patients from the first wave and 272 (40.54%) as patients from the second wave. Significantly more patients received steroids (86.4% vs 47.9%, p < 0.001), remdesivir (59.6% vs 9.5%, p < 0.001), humidified high-flow nasal cannula (18% vs 6.5%, p < 0.001), and noninvasive ventilation (11.8% vs 3.3%, p < 0.001) during the second wave. Patients from the first wave had a greater hazard for death compared with patients from the second wave (hazard ratio [HR] 1.62, 95% CI 1.08-2.43; p = 0.019). Conclusion: Among patients hospitalized with COVID-19 in our community hospital, there was a decrease in case-fatality rate in the second surge of the COVID-19 pandemic compared with the first wave.

An mRNA vaccine to prevent genital herpes.

The rapid development of two nucleoside-modified mRNA vaccines that are safe and highly effective against coronavirus disease 2019 has transformed the vaccine field. The mRNA technology has the advantage of accelerated immunogen discovery, induction of robust immune responses, and rapid scale up of manufacturing. Efforts to develop genital herpes vaccines have been ongoing for 8 decades without success. The advent of mRNA technology has the potential to change that narrative. Developing a genital herpes vaccine is a high public health priority. A prophylactic genital herpes vaccine should prevent HSV-1 and HSV-2 genital lesions and infection of dorsal root ganglia, the site of latency. Vaccine immunity should be durable for decades, perhaps with the assistance of booster doses. While these goals have been elusive, new efforts with nucleoside-modified mRNA-lipid nanoparticle vaccines show great promise. We review past approaches to vaccine development that were unsuccessful or partially successful in large phase 3 trials, and describe lessons learned from these trials. We discuss our trivalent mRNA-lipid nanoparticle approach for a prophylactic genital herpes vaccine and the ability of the vaccine to induce higher titers of neutralizing antibodies and more durable CD4+ T follicular helper cell and memory B cell responses than protein-adjuvanted vaccines.

Trivalent nucleoside-modified mRNA vaccine yields durable memory B cell protection against genital herpes in preclinical models.

Nucleoside-modified mRNA vaccines have gained global attention because of COVID-19. We evaluated a similar vaccine approach for preventing a chronic, latent genital infection rather than an acute respiratory infection. We used animal models to compare an HSV-2 trivalent nucleoside-modified mRNA vaccine with the same antigens prepared as proteins, with an emphasis on antigen-specific memory B cell responses and immune correlates of protection. In guinea pigs, serum neutralizing-antibody titers were higher at 1 month and declined far less by 8 months in mRNA- compared with protein-immunized animals. Both vaccines protected against death and genital lesions when infected 1 month after immunization; however, protection was more durable in the mRNA group compared with the protein group when infected after 8 months, an interval representing greater than 15% of the animal's lifespan. Serum and vaginal neutralizing-antibody titers correlated with protection against infection, as measured by genital lesions and vaginal virus titers 2 days after infection. In mice, the mRNA vaccine generated more antigen-specific memory B cells than the protein vaccine at early times after immunization that persisted for up to 1 year. High neutralizing titers and robust B cell immune memory likely explain the more durable protection by the HSV-2 mRNA vaccine.

Development of cavitary lung disease as a long-term complication of coronavirus disease 2019 in a young previously healthy patient: a case report.

BACKGROUND: Cavities are frequent manifestations of a wide variety of pathological processes involving the lung. There has been a growing body of evidence of coronavirus disease 2019 leading to a cavitary pulmonary disease. CASE PRESENTATION: A healthy 29-year-old Filipino male presented to the hospital a couple of months after convalescence from coronavirus disease 2019 with severe pleuritic chest pain, fever, chills, and shortness of breath, and was found to have a cavitary lung lesion on chest computed tomography. While conservative management alone failed to improve the patient's condition, he ultimately underwent left lung video-assisted thoracoscopic surgery decortication. Even though the surgical pathology revealed only necrosis with dense acute inflammation and granulation tissue with no microorganisms, he gradually improved with medical therapy adjunct with surgical therapy. CONCLUSION: Documented cases of cavitary lung disease secondary to coronavirus disease 2019 have been mostly reported in the acute or subacute phase of the infection. However, clinicians should recognize this entity as a late complication of coronavirus disease 2019, even in previously healthy individuals.

Clinical Characteristics and Risk Factors for Death of Hospitalized Patients With COVID-19 in a Community Hospital: A Retrospective Cohort Study.

OBJECTIVE: To describe the clinical characteristics, outcomes, and risk factors for death of patients with coronavirus disease 2019 (COVID-19) in a community hospital setting. PATIENTS AND METHODS: This single-center retrospective cohort study included 313 adult patients with laboratory-confirmed COVID-19 admitted to a community hospital in Cook County, Illinois, from March 1, 2020, to May 25, 2020. Demographics, medical history, underlying comorbidities, symptoms, signs, laboratory findings, imaging studies, management, and progression to discharge or death data were collected and analyzed. RESULTS: Of 313 patients, the median age was 68 years (interquartile range, 59.0-78.5 years; range, 19-98 years), 182 (58.1%) were male, 119 (38%) were white, and 194 (62%) were admitted from a long-term care facility (LTCF). As of May 25, 2020, there were 212 (67.7%) survivors identified, whereas 101 (32.3%) nonsurvivors were identified. Multivariable Cox regression analysis showed increasing hazards of inpatient death associated with older age (hazard ratio [HR] 1.02; 95% CI, 1.01-1.04), LTCF residence (HR, 3.23; 95% CI, 1.68-6.20), and quick Sequential Organ Failure Assessment scores (HR, 2.59; 95% CI, 1.78-3.76). CONCLUSION: In this single-center retrospective cohort study of 313 adult patients hospitalized with COVID-19 illness in a community hospital in Cook County, Illinois, older patients, LTCF residents, and patients with high quick Sequential Organ Failure Assessment scores were found to have worse clinical outcomes and increased risk of death.

Type 2 diabetes is associated with increased risk of critical respiratory illness in patients COVID-19 in a community hospital.

BACKGROUND: Type 2 diabetes (T2D) is the leading non-communicable disease worldwide and is associated with several microvascular and macrovascular complications. Individuals with T2D are more prone to acquiring selected types of infections and are more susceptible to complications due to these infections. This study aimed to evaluate the relationship between T2D and COVID-19 in the community setting. METHODS: This was a single-center retrospective analysis that included 147 adult patients with laboratory-confirmed COVID-19 admitted to a community hospital. Demographics, medical history, symptoms and signs, laboratory findings, complications during the hospital course, and treatments were collected and analyzed. The Kaplan-Meier method was used to describe the probability of intubation in patients with T2D as compared with patients without T2D. The hazard ratio for intubation in the survival analysis was estimated using a bivariable Cox proportional-hazards model. RESULTS: Of 147 patients, 73 (49.7%) had a history of T2D. Patients with T2D had higher requirement of ICU admission (31.5% vs 12.2%; p = .004), higher incidence of ARDS (35.6% vs 16.2%, p = .007), higher rates of intubation (32.9% vs 12.2%, p = .003), and higher use neuromuscular blocking agents (23.3% vs 9.5%, p = .02). In the survival analysis at 28 days of follow-up, patients with T2D showed an increased hazard for intubation (HR 3.00; 95% CI, 1.39 to 6.46). CONCLUSION: In our patient population, patients with COVID-19 and T2D showed significantly higher ARDS incidence and intubation rates. The survival analysis also showed that after 28 days of follow-up, patients with T2D presented an increased risk for shorter time to intubation.

A Retrospective Study of Coinfection of SARS-CoV-2 and Streptococcus pneumoniae in 11 Hospitalized Patients with Severe COVID-19 Pneumonia at a Single Center.

BACKGROUND A lethal synergism between the influenza virus and Streptococcus pneumoniae has been identified. However, bacterial coinfection is considered relatively infrequent in hospitalized patients with COVID-19, and the co-prevalence of Streptococcus pneumoniae is low. MATERIAL AND METHODS We retrospectively analyzed the clinical characteristics and outcomes of patients subsequently admitted to AMITA Health Saint Francis Hospital between March 1 and June 30, 2020, with documented SARS-CoV-2 and S. pneumoniae coinfection. RESULTS We identified 11 patients with S. pneumoniae coinfection. The median age was 77 years (interquartile range [IQR], 74-82 years), 45.5% (5/11) were males, 54.5% (6/11) were white, and 90.9% (10/11) were long-term care facility (LTCF) residents. The median length of stay was 7 days (IQR, 6-8 days). Among 11 patients, 4 were discharged in stable condition and 7 had died, resulting in an inpatient mortality rate of 64%. CONCLUSIONS At our center, 11 patients with COVID-19 pneumonia who had confirmed infection with SARS-CoV-2 were diagnosed with Streptococcus pneumoniae infection while in hospital. All patients had pneumonia confirmed on imaging and a nonspecific increase in markers of inflammation. The in-hospital mortality rate of 64% (7 patients) was higher in this group than in previous reports. This study highlights the importance of monitoring bacterial coinfection in patients with viral lung infection due to SARS-CoV-2.

Performance of the quick COVID-19 severity index and the Brescia-COVID respiratory severity scale in hospitalized patients with COVID-19 in a community hospital setting.

OBJECTIVE: To evaluate the performance of the Quick COVID-19 Severity Index (qCSI) and the Brescia-COVID Respiratory Severity Scale (BCRSS) in predicting intensive care unit (ICU) admissions and in-hospital mortality in patients with coronavirus disease 2019 (COVID-19) pneumonia. METHODS: This was a retrospective cohort study of 313 consecutive hospitalized adult patients (18 years or older) with confirmed COVID-19. The area under the receiver operating characteristic curve (AUC) was used to assess the discriminatory power of the qCSI score and BCRSS prediction rule compared to the CURB-65 score for predicting mortality and intensive care unit admission. RESULTS: The overall in-hospital fatality rate was 32.3%, and the ICU admission rate was 31.3%. The CURB-65 score had the highest numerical AUC to predict in-hospital mortality (AUC 0.781) compared to the qCSI score (AUC 0.711) and the BCRSS prediction rule (AUC 0.663). For ICU admission, the qCSI score had the highest numerical AUC (AUC 0.761) compared to the BCRSS prediction rule (AUC 0.735) and the CURB-65 score (AUC 0.629). CONCLUSIONS: The CURB-65 and qCSI scoring systems showed a good performance for predicting in-hospital mortality. The qCSI score and the BCRSS prediction rule showed a good performance for predicting ICU admission.

SARS-CoV2 and Co-Infections: A Review of Two Cases.

COVID-19 infection caused by SARS-CoV2 virus is an acute respiratory illness which was declared as a pandemic by the World Health Organization. Usually, SARS-CoV2 infects independently and can cause spectrum of disease ranging from mild illness to severe progressive pneumonia, multiorgan dysfunction, and death; however, co-infections with other respiratory pathogens have been noted. Here, we present 2 fatal cases with co-infection, one with parainfluenza-4 virus and other co-infection/secondary infection with Streptococcus pneumoniae bacteria. Further studies are needed to study the effect of co-infections on morbidity and mortality of patients and establish the outcome of such infections.