The Rapidly Changing Patterns in Bacterial Co-Infections Reveal Peaks in Limited Gram Negatives during COVID-19 and Their Sharp Drop Post-Vaccination, Implying Potential Evolution of Co-Protection during Vaccine-Virus-Bacterial Interplay.

SARS-CoV-2 has caused the most devastating pandemic of all time in recent human history. However, there is a serious paucity of high-quality data on aggravating factors and mechanisms of co-infection. This study aimed to identify the trending patterns of bacterial co-infections and types and associated outcomes in three phases of the pandemic. Using quality hospital data, we have investigated the SARS-CoV-2 fatality rates, profiles, and types of bacterial co-infections before, during, and after COVID-19 vaccination. Out of 389 isolates used in different aspects, 298 were examined before and during the pandemic (n = 149 before, n = 149 during). In this group, death rates were 32% during compared to only 7.4% before the pandemic with significant association (p-value = 0.000000075). However, the death rate was 34% in co-infected (n = 170) compared to non-co-infected patients (n = 128), indicating a highly significant value (p-value = 0.00000000000088). However, analysis of patients without other serious respiratory problems (n = 28) indicated that among the remaining 270 patients, death occurred in 30% of co-infected patients (n = 150) and only 0.8% of non-co-infected (n = 120) with a high significant p-value = 0.00000000076. The trending patterns of co-infections before, during, and after vaccination showed a significant decline in Staphylococcus aureus with concomitant peaks in Gram negatives n = 149 before/n = 149 during, including Klebsiella pneumonian = 11/49 before/during, E. coli n = 10/24, A. baumannii n = 8/25, Ps. aeruginosa n = 5/16, and S. aureus 13/1. Nevertheless, in the post-vaccination phase (n = 91), gender-specific co-infections were examined for potential differences in susceptibility. Methicillin-resistant S. aureus dominated both genders followed by E. coli in males and females, with the latter gender showing higher rates of isolations in both species. Klebsiella pneumoniae declined to third place in male patients. The drastic decline in K. pneumoniae and Gram negatives post-vaccination strongly implied a potential co-protection in vaccines. Future analysis would gain more insights into molecular mimicry.

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.

Acute respiratory distress syndrome (ARDS) is one of the major problems in COVID-19 that is not well understood. ARDS is usually complicated by co-infections in hospitals. Although ARDS is inherited by Europeans and Africans, this is not clear for those from the Middle East. There are severe limitations in correlations made between COVID-19, ARDS, co-infectome, and patient demographics. We investigated 298 patients for associations of ARDS, coinfections, and patient demographics on COVID-19 patients' outcomes. Of the 149 patients examined for ARDS during COVID-19, 16 had an incidence with a higher case fatality rate (CFR) of 75.0% compared to those without ARDS (27.0%) (p value = 0.0001). The co-infectome association showed a CFR of 31.3% in co-infected patients; meanwhile, only 4.8% of those without co-infections (p value = 0.01) died. The major bacteria were Acinetobacter baumannii and Escherichia coli, either alone or in a mixed infection with Klebsiella pneumoniae. Kaplan-Meier survival analysis of COVID-19 patients with and without ARDS revealed a significant difference in the survival time of patients with ARDS (58.8 +/- 2.7 days) and without ARDS (41.9 +/- 1.8 days) (p value = 0.0002). These findings prove that increased hospital time was risky for co-infectome-induced SDRS later on. This also explained that while empiric therapy and lethal ventilations delayed the mortality in 75% of patients, they potentially did not help those without co-infection or ARDS who stayed for shorter times. In addition, the age of patients (n = 298) was significantly associated with ARDS (72.9 +/- 8.9) compared to those without it (56.2 +/- 15.1) and was irrespective of gender. However, there were no significant differences neither in the age of admitted patients before COVID-19 (58.5 +/- 15.3) and during COVID-19 (57.2 +/- 15.5) nor in the gender and COVID-19 fatality (p value 0.546). Thus, Gram-negative co-infectome potentially induced fatal ARDS, aggravating the COVID-19 outcome. These findings are important for the specific differential diagnosis of patients with and without ARDS and co-infections. Future vertical investigations on mechanisms of Gram-negative-induced ARDS are imperative since hypervirulent strains are rapidly circulating. This study was limited as it was a single-center study confined to Ha'il hospitals; a large-scale investigation in major national hospitals would gain more insights.

COVID-19 Clinical Profiles and Fatality Rates in Hospitalized Patients Reveal Case Aggravation and Selective Co-Infection by Limited Gram-Negative Bacteria.

Bacterial co-infections may aggravate COVID-19 disease, and therefore being cognizant of other pathogens is imperative. We studied the types, frequency, antibiogram, case fatality rates (CFR), and clinical profiles of co-infecting-pathogens in 301 COVID-19 patients. Co-infection was 36% (n = 109), while CFR was 31.2% compared to 9.9% in non-co-infected patients (z-value = 3.1). Four bacterial species dominated, namely, multidrug-resistant Klebsiella pneumoniae (37%, n = 48), extremely drug-resistant Acinetobacter baumannii (26%, n = 34), multidrug-resistant Eschericia. coli (18.6%, n = 24), and extremely drug-resistant Pseudomonas aeruginosa (8.5%, n = 11), in addition to other bacterial species (9.3%, n = 12). Increased co-infection of K. pneumoniae and A. baumannii was associated with increased death rates of 29% (n = 14) and 32% (n = 11), respectively. Klebsiella pneumoniae was equally frequent in respiratory and urinary tract infections (UTI), while E. coli mostly caused UTI (67%), and A. baumannii and P. aeruginosa dominated respiratory infections (38% and 45%, respectively). Co-infections correlated with advance in age: seniors ≥ 50 years (71%), young adults 21-49 years (25.6%), and children 0-20 years (3%). These findings have significant clinical implications in the successful COVID-19 therapies, particularly in geriatric management. Future studies would reveal insights into the potential selective mechanism(s) of Gram-negative bacterial co-infection in COVID-19 patients.

Bacterial Coinfection and Antibiotic Resistance Profiles among Hospitalised COVID-19 Patients.

While it is reported that COVID-19 patients are more prone to secondary bacterial infections, which are strongly linked to the severity of complications of the disease, bacterial coinfections associated with COVID-19 are not widely studied. This work aimed to investigate the prevalence of bacterial coinfections and associated antibiotic resistance profiles among hospitalised COVID-19 patients. Age, gender, weight, bacterial identities, and antibiotic sensitivity profiles were collected retrospectively for 108 patients admitted to the intensive care unit (ICU) and non-ICU ward of a single center in Saudi Arabia. ICU patients (60%) showed a significantly higher percentage of bacterial coinfections in sputum (74%) and blood (38%) samples, compared to non-ICU. Acinetobacter baumannii (56%) and Klebsiella pneumoniae (56%) were the most prevalent bacterial species from ICU patients, presenting with full resistance to all tested antibiotics except colistin. By contrast, samples of non-ICU patients exhibited infections with Escherichia coli (31%) and Pseudomonas aeruginosa (15%) predominantly, with elevated resistance of E. coli to piperacillin/tazobactam and trimethoprim/sulfamethoxazole. This alarming correlation between multi-drug resistant bacterial coinfection and admission to the ICU requires more attention and precaution with prescribed antibiotics to limit the spread of resistant bacteria and improve therapeutic management.

A Multi-Point Surveillance for Antimicrobial Resistance Profiles among Clinical Isolates of Gram-Negative Bacteria Recovered from Major Ha'il Hospitals, Saudi Arabia.

The devastating nosocomial resistance is an on-going global concern. Surveillance of resistance is crucial for efficient patient care. This study was aimed to conduct a surveillance in four major Ha'il Hospitals from September to December 2020. Using a multipoint program, records of 621 non-duplicate Gram-negative cultures were tested across 21 drugs belonging to different categories. Major species were Klebsiella pneumoniae (n = 187, 30%), E. coli (n = 151, 24.5%), Pseudomonas aeruginosa, (n = 84, 13.6%), Acinetobacter baumannii (n = 82, 13.3%), and Proteus mirabilis (n = 46, 7%). Based on recent resistance classifications, A. baumanni, P. aeruginosa, and enteric bacteria were defined as pan-resistant, extremely resistant, and multi-drug resistant, respectively. A. baumannii (35%) and K. pneumoniae (23%) dominated among coinfections in SARS-CoV2 patients. The "other Gram-negative bacteria" (n = 77, 12.5%) from diverse sources showed unique species-specific resistance patterns, while sharing a common Gram-negative resistance profile. Among these, Providencia stuartii was reported for the first time in Ha'il. In addition, specimen source, age, and gender differences played significant roles in susceptibility. Overall infection rates were 30% in ICU, 17.5% in medical wards, and 13.5% in COVID-19 zones, mostly in male (59%) senior (54%) patients. In ICU, infections were caused by P. mirabilis (52%), A. baumannii (49%), P. aeruginosa (41%), K. pneumoniae (24%), and E. coli (21%), and most of the respiratory infections were caused by carbapenem-resistant A. baumannii and K. pneumoniae and UTI by K. pneumoniae and E. coli. While impressive IC, hospital performances, and alternative treatment options still exist, the spread of resistant Gram-negative bacteria is concerning especially in geriatric patients. The high selective SARS-CoV2 coinfection by A. baumannii and K. pneumoniae, unlike the low global rates, warrants further vertical studies. Attributes of resistances are multifactorial in Saudi Arabia because of its global partnership as the largest economic and pilgrimage hub with close social and cultural ties in the region, especially during conflicts and political unrests. However, introduction of advanced inter-laboratory networks for genome-based surveillances is expected to reduce nosocomial resistances.