Interventions to control nosocomial transmission of SARS-CoV-2: a modelling study

Effective interventions to limit nosocomial transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are pivotal to maintain healthcare capacities during pandemic waves [1, 2]. During the first epidemic wave many hospitals around the world restricted visits and cancelled non-essential medical procedures in order to maintain adequate staffing levels for patients with COVID-19. In the Netherlands, specific infection control measures were implemented but nosocomial transmission may have been facilitated by temporary shortness of supplies of personal protective equipment (PPE), including gloves, goggles, face shields, gowns and (N95) masks, at the onset of the pandemic.

Indeed, healthcare workers (HCWs) experienced a higher incidence of SARS-CoV-2 infections, compared to other professions, during the first pandemic wave [3‐5]. Front-line HCWs in the UK and USA tested three times more frequently positive during the first epidemic wave than the general population after accounting for the frequency of testing [3]. Other studies from the UK and the Netherlands found higher SARS-CoV-2 incidences after the first epidemic wave among staff working in COVID-19 wards than staff working elsewhere in the hospital [5, 6]. In addition to direct contact with infectious patients, HCW-to-HCW transmission most likely also contributed to these elevated incidence rates.

Only a few studies incorporated modelling of SARS-CoV-2 transmission in healthcare settings [7‐11]. In a stochastic within-hospital model, combined with a deterministic model reflecting SARS-CoV-2 transmission in the community, PPE use by HCWs and patients in the entire hospital substantially reduced nosocomial infections, while random weekly testing of asymptomatic HCWs and patients was less effective [9]. Moreover, strict cohorting of undiagnosed patients and HCWs in small units reduced the probability that SARS-CoV-2 introduction would lead to a large outbreak. In a deterministic within-hospital susceptible-exposed-infectious-recovered (SEIR) model isolating COVID-19 patients in single rooms or bays reduced infection acquisition in patients by up to 80% [8]. The model predicted that periodic testing of HWCs would have a smaller effect on the COVID-19 patient-burden than isolating patients but could reduce HCW infections by up to 64% and lead to a reduction of staff absenteeism. Both aforementioned models assumed a time-invariant SARS-CoV-2 infectiousness and diagnostic PCR test with 100% sensitivity. An individual-based modelling study assessed the impact of different interventions for SARS-CoV-2 transmission in a non-COVID-19 hospital unit [11]. The model was calibrated to COVID-19 outbreak data in a neurosurgery hospital unit in Wuhan (January until February 2020). High-efficacy face-masks were shown to be most effective for reducing infection cases and workday loss. Reduction of contact rates had only a marginal effect on mitigating the outbreak in the long run. Another model (stochastic, individual-based, aimed at patients and HCWs in long-term care facilities (LTCF)) did incorporate a test sensitivity that varies with time since infection [7]. This model concluded that pooled testing (combining clinical specimens from multiple individuals into a single biological sample for a single RT-PCR test) was the most effective and efficient surveillance strategy for resource-limited LTCFs.

While these previous studies investigated interventions such as the PPE use, physical distancing among HCWs, various testing strategies and cohorting of patients and HCWs, the impact of contact tracing within-hospital settings has not been modelled yet. Observational evidence from 5700 HCWs in two large hospitals and 40 outpatient units in Milan, Italy, suggested that random testing (positivity rate of 2.6%) was less efficient than contact tracing (10%) [12].

In Dutch hospitals, patients and HCWs were cohorted in COVID wards, where HCWs used PPE during patient care, in addition to the basic infection control measures applied. With these measures, nosocomial transmission was considered well-controlled during the first wave of the pandemic, although outbreaks have been reported sporadically [13]. Yet, with the emergence of more transmissible variants, current infection control measures may become less effective. While COVID-19 vaccine rollout is underway, it is still unclear how they affect transmission and how their efficacy is affected by the new SARS-CoV-2 variants. We, therefore, explored the relative effectiveness of different infection prevention strategies for HCWs in hospitals in the absence of vaccination using an agent-based model of nosocomial SARS-CoV-2 transmission. First, we fitted the model to real-life data from the University Medical Center Utrecht (UMCU) during the period February–August 2020. Next, we evaluated the impact of various interventions on transmission, HCW absenteeism and test positivity as a marker of intervention efficiency for a more transmissible variant (e.g., B.1.1.7) and draw general conclusions for infection control in hospitals with a similar structure.

We observed good agreement between the number of patients in COVID wards predicted by our wild-type scenario and the real-life UMCU data during the first wave for R_S = 1.25 and R_A = 0.5. However, the model slightly overestimates hospitalizations for the second half of the first wave (Fig. 2A). We subsequently assumed the introduction of a SARS-CoV-2 variant with a 56% increase in transmissibility (based on B.1.1.7 data), resulting in R_S = 1.95 and R_A = 0.8. Keeping all other parameters the same, including HCWs using PPE in COVID wards and self-isolating at symptom onset, the total number of nosocomial transmissions increased by 303% (Fig. 2B) and the overall effective reproduction number increased by 62.5% (Fig. 2C). \( {R}_{\mathrm{S}}^{\mathrm{hcw}} \) and \( {R}_{\mathrm{S}}^{\mathrm{pat}} \) increased the most to 0.94 and 0.6, respectively (Fig. 2D), indicating that pre-symptomatic individuals pose the highest risk for onward transmissions.

During the first epidemic wave of the wild-type SARS-CoV-2 in the Netherlands, nosocomial transmission was considered to be of relative minor importance. Our results suggest that a more transmissible virus variant could significantly increase the total number of nosocomial transmissions if hospital prevention measures would not be expanded beyond those implemented during the first wave (HCWs using PPE with assumed 90% effectiveness in COVID-19 wards and self-isolating at home after symptom onset). Our findings suggest that universal PPE use in all hospital wards is the most effective intervention to reduce the reproduction number and absenteeism. These results are consistent with a previous modelling study and previous findings on significant reductions of nosocomial-acquired SARS-CoV-2 infections after implementation of universal masking policies [1, 11, 13, 34‐37].

In our model, HCW cohorting only had a small impact on nosocomial transmissions, which is due to the fact that we assumed 90% effective PPE use in the COVID wards in all scenarios. Several studies have reported elevated risks for HCWs working in COVID-19 patient care [5, 6]. Our results suggest that maintaining sufficient PPE supplies in hospital settings may reduce the need for implementing additional HCW cohorting strategies.

Our model also suggested that regular screening of HCWs could have a strong impact, but only if the test sensitivity is high throughout the infectious period. Tests with imperfect time-varying sensitivity miss many infections during the pre-symptomatic phase. Indeed, our model identified pre-symptomatically infected HCWs as drivers of transmission both to patients and to other staff. This is consistent with a descriptive study on HCWs in France where contacts causing the transmissions took place in the pre-symptomatic phase of the index case in 30% of all cases and in almost 50% of HCW-HCW transmissions [33]. Our results also agree with previous modelling studies suggesting that regular screening of HCWs was less effective than effective PPE use.

Contact tracing was highly effective in limiting nosocomial transmissions in our model, especially when traced contacts are tested at least 5 days after their exposure and precautionary measures are undertaken in the meantime. If traced HCWs are immediately tested, self-isolated and replaced by susceptible HCWs, this can lead to increased transmission, a phenomenon that was also observed by Scarpino et al. [38]. The authors used a network model and evidence from data on influenza and dengue outbreaks to show that replacing infected individuals in essential societal roles with susceptibles may lead to accelerated transmission. Our results indicate that allowing traced HCWs to work with PPE in all hospital wards is more effective in limiting transmission. Finally, our model suggests that contact tracing yields higher positivity rates than screening interventions, not only at high prevalence but also during periods of low infection rates, making this also a potentially successful and cost-effective infection control strategy in hospital settings. Our findings reinforce the recommendation by Paltansing et al to test all close contacts of a SARS-CoV-2-positive case immediately and subsequently on day 3 and 7 regardless of symptoms and to allow HCWs to work with surgical masks while awaiting their test results [13].

Our study has several limitations. First, we assumed that transmission occurs solely via HCWs in the absence of a direct patient-to-patient contact pathway, as has been used before in an individual-based model of nosocomial influenza transmission [39]. Assuming similar transmission modes for SARS-COV-2, we consider this assumption reasonable for hospital settings in Western countries where direct patient-to-patient contact is rare. When this assumption is violated, our estimated impact of HCW-based interventions is likely to be overestimated. Second, we considered SARS-CoV-2 as a cause of symptoms and neglected other respiratory tract infections. Thus, real-life positivity rates of contact tracing may be lower than presented in this study. Third, while we have included age-specific hospitalization rates for patients admitted with SARS-CoV-2 and different proportions of asymptomatic infections for HCWs and patients, we have neglected age-structure in our transmission model. A possible extension of our model would be the inclusion of age-dependent susceptibility and infectiousness parameters. However, since the considered interventions in our model are not differential with respect to age, we do not expect any impact on the relative effect of the interventions. Further, our HCW cohorting intervention scenarios assume the same degree of cohorting both for nurses and physicians. In reality, cohorting strategies are only feasible for nurses. As such, the estimated effect of this intervention is likely to be overestimated. Since the estimated effect of HCW cohorting was estimated to be small, we expect it to be even smaller when implemented in the real world. Moreover, the duration of contacts, SARS-CoV-2 reinfections, visitors or other ancillary staff, delays between symptom onset and isolation or delays between test application and test result were not included. Finally, while we identified one parameter set for which our model results fitted the available data well, it is possible that other parameter sets exist that would produce a comparable fit. We have not used formal fitting procedures to match our model results to the data given the large number of parameters. However, qualitatively, our conclusions were robust in sensitivity analyses to variation of the most important model parameters. While our model was developed using data of a large Dutch teaching hospital and of the first wave of the COVID-19 epidemic in the Netherlands, our results can be generalized to other hospitals with a similar structure and may be relevant for subsequent waves and future infectious disease outbreaks.

In conclusion, our model demonstrates that PPE use in all wards is the most effective measure to substantially reduce nosocomial spread of SARS-CoV-2 variants with higher transmissibility. However, contact tracing and regular screening using high-sensitivity tests are also effective interventions, which might be preferred in some settings.