Selective COVID-19 Coinfections in Diabetic Patients with Concomitant Cardiovascular Comorbidities Are Associated with Increased Mortality

Abstract

Coinfections and comorbidities add additional layers of difficulties into the challenges of COVID-19 patient management strategies. However, studies examining these clinical conditions are limited. We have independently investigated the significance of associations of specific bacterial species and different comorbidities in the outcome and case fatality rates among 129 hospitalized comorbid COVID-19 patients. For the first time, to best of our knowledge, we report on the predominance of Klebsiella pneumoniae and Acinetobacter baumannii in COVID-19 non-survival diabetic patients The two species were significantly associated to COVID-19 case fatality rates (p-value = 0.02186). Coinfection rates of Klebsiella pneumoniae and Acinetobacter baumannii in non-survivors were 93% and 73%, respectively. Based on standard definitions for antimicrobial resistance, Klebsiella pneumoniae and Acinetobacter baumannii were classified as multidrug resistant and extremely drug resistant, respectively. All patients died at ICU with similar clinical characterisitics. Of the 28 major coinfections, 24 (85.7%) were in non-survivor diabetic patients, implying aggravating and worsening the course of COVID-19. The rates of other comorbidities varied: asthma (47%), hypertension (79.4%), ischemic heart disease (71%), chronic kidney disease (35%), and chronic liver disease (32%); however, the rates were higher in K. pneumoniae and were all concomitantly associated to diabetes. Other bacterial species and comorbidities did not have significant correlation to the outcomes. These findings have highly significant clinical implications in the treatment strategies of COVID-19 patients. Future vertical genomic studies would reveal more insights into the molecular and immunological mechanisms of these frequent bacterial species. Future large cohort multicenter studies would reveal more insights into the mechanisms of infection in COVID-19.

A Sequent of Gram-Negative Co-Infectome-Induced Acute Respiratory Distress Syndrome Are Potentially Subtle Aggravators Associated to the SARS-CoV-2 Evolution of Virulence

“…The two pathogens, A. baumannii and K. pneumoniae , revealed aggressive profiles on patient characteristics, indicating a significant role in exacerbating the disease ( Table 1 ). This is in agreement with our previous finding that only a few Gram-negative pathogens were identified that aggravated COVID-19 clinical profiles [ 67 , 68 , 69 ]. While selective SARS-CoV-2 coinfection by limited pathogens became increasingly evident, their role in the development of stroke and ARDS remained unclear.…”

“…Therefore, from these results, we assumed that the lung injury was due to a potential cytokine storm provoked by a dynamic “infectome”. However, while cytokine storms were being reported [ 67 ] widely in the community-acquired Staphylococcus strains (CA-MRSA) during its pandemic a decade ago, their role in Gram-negatives has not yet been widely reported. To substantiate these results, stepwise investigations were necessary to confirm the influence of coinfections.…”

Biofilm-disrupting effects of phage endolysins LysAm24, LysAp22, LysECD7, and LysSi3: breakdown the matrix

“…Clinically relevant bio lms, formed by A. baumannii and K. pneumoniae species or their combination, are associated with a variety of skin and soft tissue infections, as well as nosocomial infections of the respiratory (Said et al 2022) and urinary tract (Paczosa and Mecsas 2016). Because of producing a heterogeneous and thick matrix, these causative agents possess an extreme tolerance towards various antimicrobials (Stewart 2015).…”

Co-Infection of SARS-CoV-2 and Klebsiella pneumoniae: A Systematic Review and Meta-Analysis

“…In 2022, 17 studies reported 21% co-infection with SARS-CoV-2 and Klebsiella pneumoniae [ 23 , 25 , 28 , 33 , 34 , 36 , 37 , 38 , 41 , 42 , 45 , 46 , 48 , 50 , 53 , 55 , 63 ].…”