It has been recognised for a considerable time-period, that viral respiratory infections predispose patients to bacterial infections, and that these co-infections have a worse outcome than either infection on its own. However, it is still unclear what exact roles co-infections and/or superinfections play in patients with COVID-19 infection. This was an extensive review of the current literature regarding co-infections and superinfections in patients with SARS-CoV-2 infection. The definitions used were those of the Centers for Disease Control and Prevention (US), which defines coinfection as one occurring concurrently with the initial infection, while superinfections are those infections that follow on a previous infection, especially when caused by microorganisms that are resistant, or have become resistant, to the antibiotics used earlier. Some researchers have envisioned three potential scenarios of bacterial/SARS-CoV-2 co-infection; namely, secondary SARS-CoV-2 infection following bacterial infection or colonisation, combined viral/bacterial pneumonia, or secondary bacterial superinfection following SARS-CoV-2. There are a myriad of published articles ranging from letters to the editor to systematic reviews and meta-analyses describing varying ranges of co-infection and/or superinfection in patients with COVID-19. The concomitant infections described included other respiratory viruses, bacteria, including mycobacteria, fungi, as well as other, more unusual, pathogens. However, as will be seen in this review, there is often not a clear distinction made in the literature as to what the authors are referring to, whether true concomitant/co-infections or superinfections. In addition, possible mechanisms of the interactions between viral infections, including SARS-CoV-2, and other infections, particularly bacterial infections are discussed further. Lastly, the impact of these co-infections and superinfections in the severity of COVID-19 infections and their outcome is also described. The current review describes varying rates of co-infections and/or superinfections in patients with COVID-19 infections, although often a clear distinction between the two is not clear in the literature. When they occur, these infections appear to be associated with both severity of COVID-19 as well as poorer outcomes.

/pdf/the-role-of-co-infections-and-secondary-infections-in-2dkcb9fgmb.pdf

The role of co-infections and secondary infections in patients with COVID-19

Coronavirus disease of 2019 (COVID-19) has resulted in millions of cases worldwide. As the pandemic has progressed, the understanding of this disease has evolved.This first in a two-part series on COVID-19 updates provides a focused overview of the presentation and evaluation of COVID-19 for emergency clinicians.COVID-19, caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), has resulted in significant morbidity and mortality worldwide. Several variants exist, including a variant of concern known as Delta (B.1.617.2 lineage) and the Omicron variant (B.1.1.529 lineage). The Delta variant is associated with higher infectivity and poor patient outcomes, and the Omicron variant has resulted in a significant increase in infections. While over 80% of patients experience mild symptoms, a significant proportion can be critically ill, including those who are older and those with comorbidities. Upper respiratory symptoms, fever, and changes in taste/smell remain the most common presenting symptoms. Extrapulmonary complications are numerous and may be severe, including the cardiovascular, neurologic, gastrointestinal, and dermatologic systems. Emergency department evaluation includes focused testing for COVID-19 and assessment of end-organ injury. Imaging may include chest radiography, computed tomography, or ultrasound. Several risk scores may assist in prognostication, including the 4C (Coronavirus Clinical Characterisation Consortium) score, quick COVID Severity Index (qCSI), NEWS2, and the PRIEST score, but these should only supplement and not replace clinical judgment.This review provides a focused update of the presentation and evaluation of COVID-19 for emergency clinicians. 

https://doi.org/10.1016/j.ajem.2022.01.028

Clinical update on COVID-19 for the emergency clinician: Presentation and evaluation

Mechanisms of Immunothrombosis in Vaccine-Induced Thrombotic Thrombocytopenia (VITT) Compared to Natural SARS-CoV-2 Infection.

Background and Aim: Co-infection of COVID-19 with other respiratory pathogens which may complicate the diagnosis, treatment, and prognosis of COVID-19 emerge new concern. The overlap of COVID-19 and influenza, as two epidemics at the same time can occur in the cold months of the year. The aim of current study was to evaluate the rate of such co-infection as a systematic review and meta-analysis. Methods: A systematic literature search was performed on September 28, 2019 for original research articles published in Medline, Web of Science, and Embase databases from December 2019 to September 2020 using relevant keywords. Patients of all ages with simultaneous COVID-19 and influenza were included. Statistical analysis was performed using STATA 14 software. Results: Eleven prevalence studies with total of 3,070 patients with COVID-19, and 79 patients with concurrent COVID-19 and influenza were selected for final evaluation. The prevalence of influenza infection was 0.8% in patients with confirmed COVID-19. The frequency of influenza virus co-infection among patients with COVID-19 was 4.5% in Asia and 0.4% in the America. Four prevalence studies reported the sex of patients, which were 30 men and 31 women. Prevalence of co-infection with influenza in men and women with COVID-19 was 5.3 and 9.1%, respectively. Eight case reports and 7 case series with a total of 123 patients with COVID-19 were selected, 29 of them (16 men, 13 women) with mean age of 48 years had concurrent infection with influenza viruses A/B. Fever, cough, and shortness of breath were the most common clinical manifestations. Two of 29 patients died (6.9%), and 17 out of 29 patients recovered (58.6%). Oseltamivir and hydroxychloroquine were the most widely used drugs used for 41.4, and 31% of patients, respectively. Conclusion: Although a low proportion of COVID-19 patients have influenza co-infection, however, the importance of such co-infection, especially in high-risk individuals and the elderly, cannot be ignored. We were unable to report the exact rate of simultaneous influenza in COVID-19 patients worldwide due to a lack of data from several countries. Obviously, more studies are needed to evaluate the exact effect of the COVID-19 and influenza co-infection in clinical outcomes.

/pdf/covid-19-and-influenza-co-infection-a-systematic-review-and-3kiu4l90x9.pdf

COVID-19 and Influenza Co-infection: A Systematic Review and Meta-Analysis

Infectious diseases have remained one of humanity's biggest problems for decades. Multiple disease infections, in particular, have been shown to increase the difficulty of diagnosing and treating infected people, resulting in worsening human health. For example, the presence of influenza in the population is exacerbating the ongoing COVID-19 pandemic. We formulate and analyze a deterministic mathematical model that incorporates the biological dynamics of COVID-19 and influenza to effectively investigate the co-dynamics of the two diseases in the public. The existence and stability of the disease-free equilibrium of COVID-19-only and influenza-only sub-models are established by using their respective threshold quantities. The result shows that the COVID-19 free equilibrium is locally asymptotically stable when RC<1 , whereas the influenza-only model, is locally asymptotically stable when RF<1 . Furthermore, the existence of the endemic equilibria of the sub-models is examined while the conditions for the phenomenon of backward bifurcation are presented. A generalized analytical result of the COVID-19-influenza co-infection model is presented. We run a numerical simulation on the model without optimal control to see how competitive outcomes between-hosts and within-hosts affect disease co-dynamics. The findings established that disease competitive dynamics in the population are determined by transmission probabilities and threshold quantities. To obtain the optimal control problem, we extend the formulated model by including three time-dependent control functions. The maximum principle of Pontryagin was used to prove the existence of the optimal control problem and to derive the necessary conditions for optimum disease control. A numerical simulation was performed to demonstrate the impact of different combinations of control strategies on the infected population. The findings show that, while single and twofold control interventions can be used to reduce disease, the threefold control intervention, which incorporates all three controls, will be the most effective in reducing COVID-19 and influenza in the population. 

https://doi.org/10.1016/j.physa.2022.128173

Nonlinear optimal control strategies for a mathematical model of COVID-19 and influenza co-infection

COVID-19 and bleeding at unusual locations: Report of four cases.

We report 11 cases of combined diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar nonketotic coma (HHNK) in coronavirus 2019 patients who presented to our institution in New Jersey, USA. The median age was 47 years (range 12-88 years). Out of the 11 patients, 7 were male and 4 were female. Out of 11 patients, 8 had type 2 diabetes mellitus (DM), 2 had undiagnosed DM, and 1 had type 1 DM. Presenting complaints included altered mental status, weakness, shortness of breath, cough, fever, vomiting, abdominal pain, chest pain, and foot pain. Out of 11 patients, pneumonia was diagnosed at presentation in 8 patients, while in 3 patients, chest X-ray was clear. Median value of initial glucose on presentation was 974 mg/dL (range 549-1556 mg/dL), and hemoglobin A1c on presentation was 13.8%. The median value of anion gap was 34 mEq/L. Out of the 11 patients, ketonemia was moderate in 6 patients, large in 3, and small in 2 patients. Acute kidney injury (AKI) occurred in 9 patients and 2 patients required renal replacement therapy. Out of the 11 patients, 6 required mechanical ventilation and 7 patients died. All the 6 patients requiring mechanical ventilation died. Our case series shows COVID-19 infection can precipitate acute metabolic complications in known DM patients or as first manifestation in undiagnosed DM patients. Patients can present with DKA/HHNK symptoms and/or respiratory symptoms. Mechanical ventilation is a poor prognostic factor. Further studies are needed to characterize prognostic factors associated with mortality in this vulnerable patient population.

https://journals.sagepub.com/doi/pdf/10.1177/23247096211021231

COVID-19 and Combined Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar Nonketotic Coma: Report of 11 Cases.

BACKGROUND AND OBJECTIVES: To describe the clinical characteristics and outcomes of hospitalized coronavirus disease 2019 (COVID-19) patients with diabetic ketoacidosis (DKA) -- a single center tertiary hospital experience MATERIALS AND METHODS: A retrospective study was conducted among patients admitted to our hospital in the United States between March 1st and June 15th, 2020 with DKA and severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection known as COVID-19 We compared the baseline characteristics, laboratory data, and clinical course between survivors and nonsurvivors to identify the risk factors associated with mortality in the patients with DKA RESULTS: A total number of 43 patients were included in this study The median age was 52 years Thirty-three (76 7%) patients were male Median value of initial glucose on presentation was 553 mg/dL (300 0-1927 0 mg/dL) On admission, 33 (76 7%) patients had glycated hemoglobin (HbA1c)>=8% (64 mmol/mol) and HbA1cwas not obtained in 10 (23 3%) patients Acute kidney injury (AKI) was seen in 37 (86 0%) patients, 6 (14%) patients required renal replacement therapy and 22 (51 2%) required mechanical ventilation Among the 43 patients, 25 (58 1%) died Out of 25 patients who died 15 (60 0%) were Hispanics, 6 (24 0%) were White, 3 (12 0%) were African American, 1 (4%) was Arabic, and 1 (4%) was Asian The patients who died were older in age than who survived (mean age 58 +/- 6 13 vs 46 +/- 9 39;p = 0 023) Some 95% of the patients requiring mechanical ventilation died (odds ratio [OR]: 89 25;95% confidence interval [CI]: 9 10-874 96);p=0 001) Compared to survivors, nonsurvivors had significantly higher d-dimer (13 00 +/- 3 20 mcg/mL vs 6 15 +/- 3 66 mcg/mL;p< 0 006) and peak ferritin values (2763 66 +/- 1105 32 ng/mL vs 835 16 +/- 257 07 ng/mL;p= 0 016) Conclusion: Our retrospective study shows COVID-19 infection may present as DKA in patients with diabetes mellitus (DM) Older age, mechanical ventilation, elevated d-dimer, and ferritin are associated with poor prognosis in these patients Our study shows that COVID-19 is associated with substantial mortality in DKA patients and adds to the limited literature available regarding poor risk factors associated with mortality in these patients

COVID-19 and Diabetic Ketoacidosis: A Single Center Experience

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus responsible for the current global pandemic, coronavirus disease 2019 (COVID-19) COVID-19 usually presents with respiratory symptoms but can affect multiple organ systems A wide spectrum of complications can occur depending upon the comorbidities of patients There is limited literature available regarding the presentation and outcome of COVID-19 in chronic lymphocytic leukaemia (CLL) patients We report 2 cases of COVID-19-induced hyperleucocytosis (WBC count >100,000/mul) in CLL patients LEARNING POINTS: Lymphopenia has been associated with severe disease and is a poor prognostic factor in COVID-19 infected patients;however, our cases show COVID-19-induced hyperleucocytosis (WBC count >100,000/mul)/lymphocytosis in CLL patients Prior reports suggest that ibrutinib may have a protective effect against COVID-19 by decreasing inflammation and preventing progression to ARDS

COVID-19-Induced Hyperleucocytosis in Chronic Lymphocytic Leukaemia

Although cytomegalovirus (CMV) encephalitis is a common viral infection, it is rarely reported in immunocompromised patients with cluster of differentiation four (CD4) cell counts greater than 50. Herein, we present a case of CMV encephalitis co-infected with Epstein-Barr virus (EBV) in a human immunodeficiency virus (HIV) patient with a CD4 cell count of 145. In addition, the patient was also infected with syphilis and tuberculosis. This case report will discuss the complications of untangling the differential diagnosis in an immunocompromised host with multiple infections, specifically, how it was difficult to identify the exact etiology of this patient's encephalopathy. We will address the plausible explanations for this unusual presentation, including CD4 dysfunction, latent and re-infections, and synergism seen with the co-infections in HIV patients.

A Case of Cytomegalovirus Encephalitis in Cluster of Differentiation Four Cell Counts Greater Than 50.

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