Brigham and Women's Hospitals

Infectious Disease

Updated: July 28, 2020

Diagnostics

  1. BWH-specific inpatient COVID-19 testing pathways and infection control guidelines can be found here (Partners login required)
  2. Please reference the Diagnostics chapter

Biothreats, Flags and Infection Control

  1. Please see the Biothreats section and Infection Control section for further details
  2. Testing and Infection Control Guidelines (Partners login required)

Infectious Diseases Consultation

  1. Infectious diseases should be consulted on all inpatients who have been diagnosed with COVID-19 and are being considered for treatment
  2. Infectious diseases e-consults are available for outpatients

COVID-19 Treatment with Antivirals

  1. A breakdown of the potential therapeutic options for COVID-19 can be found in the Therapeutics chapter
  2. The BWH Infectious Diseases COVID-19 treatment guidelines can be used to access current BWH protocols based on enrolling clinical trials (available on-site or off-site via VPN)

Secondary Infections

  1. Available data on secondary infections in COVID-19 are limited. To date, viral co-infection data suffers from inconsistencies.
  1. A study in San Francisco found ~20% of symptomatic COVID-19 patients were also PCR positive for another viral pathogen (Kim et al, JAMA, 2020)
  2. In contrast, two studies in San Francisco and Wuhan, China where hospitalized COVID-19 patients tested for influenza and RSV found that none of these patients had evidence of viral co-infection (Myers et al, JAMA, 2020; Chen et al, Lancet, 2020)
  3. A meta-analysis of 1014 hospitalized COVID-19 patients found a viral co-infection rate of 3% (95% CI 1-6%, I2=62.3%), with RSV and influenza being the most common coinfections (Lansbury et al, J Infect, 2020)
  1. The incidence of nosocomial infections is 7-8% among hospitalized COVID-19 patients
  1. One meta-analysis of 2183 hospitalized COVID-19 patients found 7% had a bacterial coinfection (95% CI 3-12%, I2=92.2%) (Lansbury et al, J Infect, 2020)
  2. Another meta-analysis of 806 hospitalized COVID-19 patients found 8% developed bacterial and/or fungal infections during admission (Rawson et al, Clin Infect Dis, 2020).
  3. A separate meta-analysis of 3448 COVID-19 patients broke bacterial infections down into co-infection and secondary infection and found the risk of co-infection on presentation to be 3.5%, while the risk of secondary infection after presentation was 15.5%. In this same cohort, 71.3% of patients received antibiotics, despite only 7.1% of patients overall having a bacterial infection (Langford et al, Clin Microbiol Infect, 2020)
  4. Two smaller cohort studies have reported similar nosocomial infection rates - 8% of 150 hospitalized patients (Ruan et al, Intensive Care Med, 2020) and 13.5% of 52 mechanically ventilated patients (Yang et al, Lancet Resp Med, 2020). In contrast, one study of 339 COVID-19 patients over 60 years of age with severe and critical disease found bacterial secondary infection rates of 42.8% (Wang et al, J Infect, 2020)
  5. The most common reported infections are pneumonia (32%), bacteremia (24%), and urinary tract infections (22%) (He et al, Infect Control Hosp Epidemiol, 2020)
  1. Nosocomial infections are associated with increased COVID-19 severity and death
  1. There is a strong association between nosocomial infection and mortality (He et al, Infect Control Hosp Epidemiol, 2020; Wang et al, J Infect, 2020)
  2. In one study, patients with severe COVID-19 suffered a higher rate of secondary infection compared to those with non-severe COVID-19 (Zhang et al, J Clin Virol, 2020)
  1. Organisms reported included those commonly seen with hospital-acquired infections
  1. Bacterial pathogens include Mycoplasma sp., Haemophilus influenzae, Pseudomonas aeruginosa, Klebsiella sp., Enterobacter sp., Staphylococcus aureus, Acinetobacter sp., and E.coli, and vancomycin-resistant Enterococcus sp. (Langford et al, Clin Microbiol Infect, 2020; Lansbury et al, J Infect, 2020)
  2. Fungal pathogens such as Aspergillus sp., Candida albicans, and Pneumocystis jirovecii have been described in a subset of patients (Lansbury et al, J Infect, 2020; Menon et al, Am J Respir Crit Care Med, 2020)
  1. In a prospective Italian cohort of 108 mechanically ventilated COVID-19 patients, probable pulmonary aspergillosis was diagnosed in 30 patients (27.7%) after a median of 4 days from ICU admission, and these patients had a much higher risk of 30-day mortality (OR 3.53 (95% CI 1.29-9.67, p=0.014). Of note, most patients received tocilizumab or steroids in this cohort (Bartoletti et al, Clin Infect Dis, 2020)
  2. Some case series have reported COVID-19 associated pulmonary aspergillosis rates of 20-35% (Arastehfar et al, J Fungi, 2020), while others are as low as 3.8% (Lamoth et al, Clin Microbiol Infect, 2020)
  1. Risk factors for secondary bacterial and fungal infections
  1. In a single center study of 65 COVID-19 patients, invasive devices (OR 4.28, 95% CI: 2.47–8.61), diabetes (OR 3.06, 95% CI: 1.41–7.22), and the use of one or more class of antibiotic (OR 1.84, 95% CI: 1.31–4.59) were significant predictors of nosocomial infection (He et al, Infect Control Hosp Epidemiol, 2020
  2. Glucocorticoid treatment (38% in He et al, Infect Control Hosp Epidemiol, 2020) was also found to be positively associated with secondary infection
  3. There is a disproportionate high use of antibiotics despite paucity of evidence for bacterial secondary infection (He et al, Infect Control Hosp Epidemiol, 2020; Zhou et al, Infect Control Hosp Epidemiol, 2020; Rawson et al, Clin Infect Dis, 2020)
  1. Empiric antibiotic and antifungal treatment should not be standard of care
  1. 75% of patients who developed secondary bacterial or fungal infection were already receiving prophylactic antibiotics. This suggests prophylactic agents may not prevent hospital-acquired infections and risk selecting for more drug-resistant pathogens (He et al, Infect Control Hosp Epidemiol, 2020)

Antibiotics

Choice of agent

  1. Clinical reports indicate that rates of bacterial superinfection with COVID-19 are low (see Secondary Infections section above), but when present, increase mortality risk. Anecdotal reports suggest less MRSA superinfection than is often seen with influenza. Unnecessary antibiotics carry risks of fluid overload and drug-resistance, as well as the possibility that antibiotics may become a limited resource. (Zhou et al, Lancet, 2020; Yang et al, Lancet Respir Med, 2020; Lippi and Plebani, Clin Chim Acta, 2020; WHO, COVID-19 Interim guidance, May 2020).
  2. If antibiotics are to be used, they should reflect IDSA guidelines based on presumed source and MDRO risk factors
  1. For empiric coverage for a presumed pulmonary source of infection:
  1. In patients without risk factors for MRSA or Pseudomonas (i.e., living in community, no prior MDROs), initiate ceftriaxone and azithromycin
  2. In patients with risk factors for MRSA or Pseudomonas (i.e., chronic hospitalization, prior MDR infections), obtain a respiratory culture and a MRSA nares screen and initiate cefepime and vancomycin. Ciprofloxacin may be considered if high concern for Pseudomonas aeruginosa
  1. See special dispensations for oncology patients in “Oncology”

Formulation

  1. Give oral antibiotics (azithromycin, levofloxacin, ciprofloxacin, etc.) when possible to reduce volume load, unless concerns for poor oral absorption

Discontinuation

  1. Unnecessary antibiotics should be discontinued as soon as possible (ideally, within 48 hours) upon culture maturation. Clinical judgement should prevail over any specific lab value, but we suggest discontinuing when the following criteria are met:
  1. Clinical status is not deteriorating
  2. Cultures do not reveal pathogens at 48 hours and/or procalcitonin and WBC are relatively stable from 0 to 48 hours

Outpatient Management

  1. Please see the Ambulatory COVID Management section

HIV-Positive Patients

  1. While data continue to emerge on this topic, the interaction between HIV and SARS-CoV-2 remains poorly defined and is likely complex
  2. It remains unclear if, and how, HIV infection affects risk or severity of COVID-19
  1. Multiple studies from New York City (Richardson et al, JAMA, 2020; Sigel et al, Clin Infect Dis, 2020; Karmen-Tuohy et al, J Acquir Immune Defic Syndr, 2020), Spain (Vizcarra et al, Lancet HIV, 2020), and China (Guo et al, unpublished report, 2020) have found that HIV-positive patients develop COVID-19 at a similar rate as the general population. The patients included in these studies were largely on antiretroviral therapy (ART) with well-controlled HIV
  2. A large Spanish cohort study of people with well-controlled HIV found that the rate of COVID-19 diagnosis and hospitalization in HIV patients was decreased to 30.0 cases per 10,000, compared with 41.7 per 10,000 in the general population (Del Amo et al, Annals Intern Med, 2020).
  3. There is very limited data on COVID-19 patients with poorly controlled HIV or AIDS. A recent unpublished study examined public healthcare data in South Africa, which has the highest rate of HIV in the world at about 20%, with only about ⅔ of those on ART (UNAIDS). In this population, HIV infection conferred an adjusted hazard ratio of 2.75 for risk of death from COVID-19 (Davies M, presentation on behalf of Western Cape Department of Health). Detailed information, including the number of participants, CD4+ T cell counts, HIV viral loads, and ART treatment status, has not yet been made available
  1. Some antiretroviral therapy may be protective against COVID-19
  1. A large Spanish cohort study of over 77,000 people with HIV, 236 of whom were diagnosed with COVID-19, found that patients taking tenofovir disproxil fumarate (TDF)/emtricitabine (FTC) had a significantly decreased risk of COVID-19 diagnosis and hospitalization compared with those taking tenofovir alafenamide (TAF)/FTC or abacavir (ABC)/lamivudine (3TC). This may be an effect of increased blood concentrations of tenofovir with TDF compared with TAF, though may also reflect that patients taking TDF are typically younger and healthier than those on TAF (Del Amo et al, Annals Intern Med, 2020)
  2. Conversely, a smaller observational Spanish study of 2873 HIV-positive individuals, 51 of whom had COVID-19, found that tenofovir (either TDF or TAF) use was disproportionately enriched among COVID-19 cases (Vizcarra et al, Lancet HIV, 2020)
  3. A randomized controlled trial of lopinavir-ritonavir in treatment of severe COVID-19 in hospitalized, HIV-negative patients found no benefit (Cao et al., NEJM 2020). This treatment also did not reduce duration of viral shedding in mild COVID-19 in a Taiwanese study (Cheng et al, J Microbiol Immunol Infect, 2020)
  4. For further information about antiretroviral agents under investigation for treatment of COVID-19, please see the Therapeutics Chapter
  1. There is speculation that lymphopenia and immune dysfunction in HIV-positive individuals may protect from the hyperinflammatory state thought to contribute to severe COVID-19 disease (Mascolo et al, J Med Virol, 2020), but no evidence currently exists to support this theory
  2. Summary and recommendations:
  1. Studies to date suggest that well-controlled HIV does not substantially increase the risk or severity of COVID-19, but data on patients with low CD4+ counts remains sparse. Given the limitations of the existing evidence at this time, we recommend that HIV-positive patients be considered high risk, in accordance with existing CDC guidelines, and be counseled on precautions accordingly
  2. Per existing standard of care, all patients with HIV should remain on a daily ART regimen under the supervision of a trained HIV provider
  3. We do not recommend changing an existing ART regimen for the purposes of prophylaxis or treatment of COVID-19 in HIV-positive patients
  4. HIV-positive patients who develop COVID-19 do not require any change from standard protocol in management or treatment strategies