Current and Emerging Therapies for COVID-19 in Lung Transplantation.

Purpose of Review: The landscape of the coronavirus disease 2019 (COVID-19) pandemic has rapidly changed over the past 3 years. Paralleling this evolution, the scientific and medical communities have reported many novel findings relating to the infection's epidemiology, transmission, diagnosis, and treatment. We review pertinent studies of COVID-19 therapeutics with an emphasis on their application to lung transplant recipients. Recent Findings: Agents that have been well-studied for treating COVID-19 include antivirals (remdesivir, nirmatrelvir/ritonavir, molnupiravir), monoclonal antibodies, and immunomodulators (for example, corticosteroids and tocilizumab). Summary: Remdesivir remains an essential therapy for managing mild-moderate COVID-19. Though highly efficacious for mild-moderate COVID-19 for outpatient therapy, ritonavir-boosted nirmatrelvir has limited use in lung transplant recipients due to significant drug-drug interactions. Monoclonal antibodies, though useful, are the most affected by the emergence of new viral variants.

Remdesivir Use in the Setting of Severe Renal Impairment: A Theoretical Concern or Real Risk?

BACKGROUND: Remdesivir (RDV) is US FDA approved for coronavirus disease 2019 (COVID-19) but not recommended in severe renal impairment (SRI, Creatinine clearance <30mL/min or requiring renal replacement therapy). Few studies have evaluated RDV in patients with SRI. METHODS: Hospitalized patients who received RDV between 1 May 2020 and 31 October 2020 were analyzed in a retrospective chart review. We compared incident adverse events (AEs) in patients with and without SRI, including hepatotoxicity, nephrotoxicity, any reported AE, mortality, and length of stay. RESULTS: Of a total of 135 patients, 20 had SRI. Patients with SRI were significantly older (70 vs 54 years, P = .0001). The incidence of possible AEs was 30% among those with SRI vs 11% without (P = .06). Liver function test (LFT) elevations occurred in 10% vs 4% (P = .28), and serum creatinine (SCr) elevations in 27% vs 6% (P = .02) of patients with SRI vs without, respectively. LFT and SCr elevations were not attributed to RDV in either group. Mortality and length of stay were consistent with historical controls. CONCLUSIONS: RDV AEs occurred infrequently and overall were not significantly different between those with and without SRI. While more of patients with SRI experienced SCr elevations, 3 (75%) patients had acute kidney injury prior to RDV. The use of RDV in this small series of patients with SRI appeared to be relatively safe, and the potential benefit outweighed the theoretical risk of liver or renal toxicity. Additional studies are needed to confirm this finding.

COVIDOSE: A Phase II Clinical Trial of Low-Dose Tocilizumab in the Treatment of Noncritical COVID-19 Pneumonia.

Interleukin-6 (IL-6)-mediated hyperinflammation may contribute to the mortality of coronavirus disease 2019 (COVID-19). The IL-6 receptor-blocking monoclonal antibody tocilizumab has been repurposed for COVID-19, but prospective trials and dose-finding studies in COVID-19 have not yet fully reported. We conducted a single-arm phase II trial of low-dose tocilizumab in nonintubated hospitalized adult patients with COVID-19, radiographic pulmonary infiltrate, fever, and C-reactive protein (CRP) ≥ 40 mg/L. We hypothesized that doses significantly lower than the emerging standards of 400 mg or 8 mg/kg would resolve clinical and laboratory indicators of hyperinflammation. A dose range from 40 to 200 mg was evaluated, with allowance for one repeat dose at 24 to 48 hours. The primary objective was to assess the relationship of dose to fever resolution and CRP response. Thirty-two patients received low-dose tocilizumab, with the majority experiencing fever resolution (75%) and CRP decline consistent with IL-6 pathway abrogation (86%) in the 24-48 hours following drug administration. There was no evidence of a relationship between dose and fever resolution or CRP decline over the dose range of 40-200 mg. Within the 28-day follow-up, 5 (16%) patients died. For patients who recovered, median time to clinical recovery was 3 days (interquartile range, 2-5). Clinically presumed and/or cultured bacterial superinfections were reported in 5 (16%) patients. Low-dose tocilizumab was associated with rapid improvement in clinical and laboratory measures of hyperinflammation in hospitalized patients with COVID-19. Results of this trial provide rationale for a randomized, controlled trial of low-dose tocilizumab in COVID-19.

Clinical Sensitivity of Severe Acute Respiratory Syndrome Coronavirus 2 Nucleic Acid Amplification Tests for Diagnosing Coronavirus Disease 2019.

Utilizing 34 348 severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) nucleic acid amplification test (NAAT) results from 2 health systems, we estimated the clinical sensitivity of a single SARS-CoV-2 NAAT. We found that SARS-CoV-2 NAAT has 82%-97% sensitivity for diagnosing coronavirus disease 2019 among symptomatic patients.

Three-Tiered COVID-19 Cohorting Strategy and Implications for Memory-Care.

An outbreak of SARS-CoV-2 in a skilled nursing facility (SNF) can be devastating for residents and staff. Difficulty identifying asymptomatic and presymptomatic cases and lack of vaccination or treatment options make management challenging. We created, implemented, and now present a guide to rapidly deploy point-prevalence testing and 3-tiered cohorting in an SNF to mitigate an outbreak. We outline key challenges to SNF cohorting.