COVID-19 pandemic responses may impact the spread of antibiotic-resistant bacteria: a modelling study (preprint)

COVID-19 pandemic responses have dramatically modified the global ecological and epidemiological landscape of many infectious diseases. However, the pandemics impacts on antimicrobial resistance (AMR) are currently poorly understood and lack data. While surges in COVID-19 cases during the first wave of the pandemic may have exacerbated AMR, decreases in antibiotic use may have had the opposite effect. To disentangle how pandemic impacts such as lockdowns and modified antibiotic prescribing may affect AMR, we developed a mathematical model formalizing simultaneous transmission of SARS-CoV-2 and colonization with a bacterial pathogen across six pandemic scenarios. We used simulation to assess the effect of each scenario on the bacterial carriage prevalence, antibiotic resistance rate, and the invasive bacterial disease (IBD) incidence, using parameters based on the commensal community bacterium Streptococcus pneumoniae. Pandemic scenarios without community-wide lockdowns all resulted in a decrease in carriage prevalence of antibiotic-sensitive bacteria and an increase in the prevalence of antibiotic-resistant bacteria, while the addition of a population-wide lockdown resulted in a large reduction in colonization prevalence and IBD incidence for both strains (>70%). This translated to an increase in the antibiotic resistance rate across all scenarios to varying degrees, with lingering effects after the cessation of COVID-19 response measures. In the absence of lockdown, a population-wide surge in antibiotic prescribing coincident with the peak in SARS-CoV-2 infection resulted in the greatest increases in resistance rate (23%) and resistant IBD incidence (6%). Within-host interactions, SARS-CoV-2 variants, and population immunity are found to further drive the magnitude of pandemic impacts on resistant IBD incidence. Sensitivity analyses suggest that the extent of such impacts likely varies across different bacterial species. Although real-life scenarios are significantly more complicated, our findings suggest that COVID-19 pandemic responses may significantly impact antibiotic resistance in the community and support the need for monitoring resistance during pandemic waves.

The interactions of SARS-CoV-2 with co-circulating pathogens: Epidemiological implications and current knowledge gaps (preprint)

Despite the availability of effective vaccines, the persistence of SARS-CoV-2 suggests that co-circulation with other pathogens and resulting multi-epidemics -- such as twindemics of COVID-19 and influenza -- will become increasingly frequent. To better forecast and control the risk of such multi-epidemics, it is essential to elucidate the potential interactions of SARS-CoV- 2 with other pathogens; these interactions, however, remain poorly defined. Here, we aimed to review the current body of evidence about SARS-CoV-2 interactions. To study pathogen interactions in a systematic way, we first developed a general framework to capture their major components - namely, sign, strength, symmetry, duration, and mechanism. We then reviewed the experimental evidence from animal models about SARS-CoV-2 interactions. The studies identified demonstrated that SARS-CoV-2 and influenza A virus co-infection increased disease severity compared with mono-infection. By contrast, the effect of previous or co-infection on viral load of either virus was inconsistent across studies. Next, we reviewed the epidemiological evidence about SARS-CoV-2 interactions in human populations. Although numerous studies were identified, only few were specifically designed to infer interaction and many were prone to bias and confounding. Nevertheless, their results suggested that influenza and pneumococcal conjugate vaccinations were associated with reduced risk, and earlier influenza infection with increased risk, of SARS-CoV-2 infection and severe COVID-19. Finally, we formulated simple transmission models of SARS-CoV-2 co-circulation with a virus or a bacterium, showing how they can naturally incorporate the proposed framework. More generally, we propose that such models, when designed with an integrative and multidisciplinary perspective, will be invaluable tools in studying SARS-CoV-2 interactions with other pathogens.

Characteristics and Outcomes of Patients with Acute Coronary Syndrome and COVID-19

Acute coronary syndrome (ACS) in patients with COVID-19 is triggered by various mechanisms and can significantly affect the patient's further treatment and prognosis. The study aimed to investigate the characteristics, major complications, and predictors of mortality in COVID-19 patients with ACS. All consecutive patients hospitalized from 5 July 2020 to 5 May 2021 for ACS with confirmed SARS-Co-2 were prospectively enrolled and tracked for mortality until 5 June 2021. Data from the electronic records for age and diagnosis, matched non-COVID-19 and COVID-19 ACS group, were extracted and compared. Overall, 83 COVID-19 ACS patients, when compared to 166 non-COVID ACS patients, had significantly more prevalent comorbidities, unfavorable clinical characteristics on admission (acute heart failure 21.7% vs. 6.6%, p < 0.01) and higher rates of major complications, 33.7% vs. 16.8%, p < 0.01, and intrahospital 30-day mortality, 6.7% vs. 26.5%, p < 0.01. The strongest predictors of mortality were aortic regurgitation, HR 9.98, 95% CI 1.88;52.98, p < 0.01, serum creatinine levels, HR 1.03, 95% CI 1.01;1.04, p < 0.01, and respiratory failure therapy, HR 13.05, 95% CI 3.62;47.01, p < 0.01. Concomitant ACS and COVID-19 is linked to underlying comorbidities, adverse presenting features, and poor outcomes. Urgent strategies are needed to improve the outcomes of these patients.

The impact of co-circulating pathogens on SARS-CoV-2/COVID-19 surveillance: How concurrent epidemics may decrease true SARS-CoV-2 percent positivity (preprint)

Background Circulation of non-SARS-CoV-2 respiratory viruses during the COVID-19 pandemic may alter quality of COVID-19 surveillance, with possible consequences for real-time analysis and delay in implementation of control measures. Here, we assess the impact of an increased circulation of other respiratory viruses on the monitoring of positivity rates of SARS-CoV-2 and interpretation of surveillance data. Methods Using a multi-pathogen Susceptible-Exposed-Infectious-Recovered (SEIR) transmission model formalizing co-circulation of SARS-CoV-2 and another respiratory we assess how an outbreak of secondary virus may inflate the number of SARS-CoV-2 tests and affect the interpretation of COVID-19 surveillance data. Using simulation, we assess to what extent the use of multiplex PCR tests on a subsample of symptomatic individuals can support correction of the observed SARS-CoV-2 percent positive during other virus outbreaks and improve surveillance quality. Results Model simulations demonstrated that a non-SARS-CoV-2 epidemic creates an artificial decrease in the observed percent positivity of SARS-CoV-2, with stronger effect during the growth phase, until the peak is reached. We estimate that performing one multiplex test for every 1,000 COVID-19 tests on symptomatic individuals could be sufficient to maintain surveillance of other respiratory viruses in the population and correct the observed SARS-CoV-2 percent positive. Conclusions This study highlights that co-circulating respiratory viruses can disrupt SARS-CoV-2 surveillance. Correction of the positivity rate can be achieved by using multiplex PCR, and a low number of samples is sufficient to avoid bias in SARS-CoV-2 surveillance. Summary COVID-19 surveillance indicators may be impacted by increased co-circulation of other respiratory viruses delaying control measure implementation. Continued surveillance through multiplex PCR testing in a subsample of the symptomatic population may play a role in fixing this problem.