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1.
Clin Infect Dis ; 2021 Oct 01.
Article in English | MEDLINE | ID: covidwho-2017765

ABSTRACT

BACKGROUND: Remdesivir (RDV) improved clinical outcomes among hospitalized COVID-19 patients in randomized trials, but data from clinical practice are limited. METHODS: We examined survival outcomes for US patients hospitalized with COVID-19 between Aug-Nov 2020 and treated with RDV within two-days of hospitalization vs. those not receiving RDV during their hospitalization using the Premier Healthcare Database. Preferential within-hospital propensity score matching with replacement was used. Additionally, patients were also matched on baseline oxygenation level (no supplemental oxygen charges (NSO), low-flow oxygen (LFO), high-flow oxygen/non-invasive ventilation (HFO/NIV) and invasive mechanical ventilation/ECMO (IMV/ECMO) and two-month admission window and excluded if discharged within 3-days of admission (to exclude anticipated discharges/transfers within 72-hrs consistent with ACTT-1 study). Cox Proportional Hazards models were used to assess time to 14-/28-day mortality overall and for patients on NSO, LFO, HFO/NIV and IMV/ECMO. RESULTS: 28,855 RDV patients were matched to 16,687 unique non-RDV patients. Overall, 10.6% and 15.4% RDV patients died within 14- and 28-days, respectively compared with 15.4% and 19.1% non-RDV patients. Overall, RDV was associated with a reduction in mortality at 14-days (HR[95% CI]: 0.76[0.70-0.83]) and 28-days (0.89[0.82-0.96]). This mortality benefit was also seen for NSO, LFO and IMV/ECMO at 14-days (NSO:0.69[0.57-0.83], LFO:0.68[0.80-0.77], IMV/ECMO:0.70[0.58-0.84]) and 28-days (NSO:0.80[0.68-0.94], LFO:0.77[0.68-0.86], IMV/ECMO:0.81[0.69-0.94]). Additionally, HFO/NIV RDV group had a lower risk of mortality at 14-days (0.81[0.70-0.93]) but no statistical significance at 28-days. CONCLUSIONS: RDV initiated upon hospital admission was associated with improved survival among COVID-19 patients. Our findings complement ACTT-1 and support RDV as a foundational treatment for hospitalized COVID-19 patients.

2.
Clin Pharmacol Ther ; 2022 Jul 07.
Article in English | MEDLINE | ID: covidwho-1919261

ABSTRACT

AZD7442 (Evusheld) is a combination of two human anti-severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs), tixagevimab (AZD8895) and cilgavimab (AZD1061). Route of administration is an important consideration to improve treatment access. We assessed pharmacokinetics (PKs) of AZD7442 absorption following 600 mg administered intramuscularly (i.m.) in the thigh compared with 300 mg intravenously (i.v.) in ambulatory adults with symptomatic COVID-19. PK analysis included 84 of 110 participants randomized to receive i.m. AZD7442 and 16 of 61 randomized to receive i.v. AZD7442. Serum was collected prior to AZD7442 administration and at 24 hours and 3, 7, and 14 days later. PK parameters were calculated using noncompartmental methods. Following 600 mg i.m., the geometric mean maximum concentration (Cmax ) was 38.19 µg/mL (range: 17.30-60.80) and 37.33 µg/mL (range: 14.90-58.90) for tixagevimab and cilgavimab, respectively. Median observed time to maximum concentration (Tmax ) was 7.1 and 7.0 days for tixagevimab and cilgavimab, respectively. Serum concentrations after i.m. dosing were similar to the i.v. dose (27-29 µg/mL each component) at 3 days. The area under the concentration-time curve (AUC)0-7d geometric mean ratio was 0.9 for i.m. vs. i.v. Participants with higher weight or body mass index were more likely to have lower concentrations with either route. Women appeared to have higher interparticipant variability in concentrations compared with men. The concentrations of tixagevimab and cilgavimab after administration i.m. to the thigh were similar to those achieved with i.v. after 3 days from dosing. Exposure in the i.m. group was 90% of i.v. over 7 days. Administration to the thigh can be considered to provide consistent mAb exposure and improve access.

3.
Cell Rep Med ; 3(7): 100678, 2022 07 19.
Article in English | MEDLINE | ID: covidwho-1895506

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs) are among the treatments recommended for high-risk ambulatory persons with coronavirus 2019 (COVID-19). Here, we study viral culture dynamics post-treatment in a subset of participants receiving the mAb bamlanivimab in the ACTIV-2 trial (ClinicalTrials.gov: NCT04518410). Viral load by qPCR and viral culture are performed from anterior nasal swabs collected on study days 0 (day of treatment), 1, 2, 3, and 7. Treatment with mAbs results in rapid clearance of culturable virus. One day after treatment, 0 of 28 (0%) participants receiving mAbs and 16 of 39 (41%) receiving placebo still have culturable virus (p < 0.0001). Recrudescence of culturable virus is detected in three participants with emerging mAb resistance and viral RNA rebound. While further studies are necessary to fully define the relationship between shed culturable virus and transmission, these results raise the possibility that mAbs may offer immediate (household) and public-health benefits by reducing onward transmission.


Subject(s)
COVID-19 , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antibodies, Neutralizing , COVID-19/drug therapy , Humans , SARS-CoV-2
4.
Am J Infect Control ; 2022 Jun 13.
Article in English | MEDLINE | ID: covidwho-1885586

ABSTRACT

To evaluate the co-circulation of respiratory viruses during the SARS-CoV-2 Alpha surge, we performed a molecular respiratory panel on 1,783 nasopharyngeal swabs collected between January 15 and April 15, 2021, from symptomatic outpatients that tested negative for SARS-CoV-2 in North Carolina. Of these, 373 (20.9%) were positive for at least 1 virus tested on the panel. Among positive tests, over 90% were positive for rhinovirus and/or enterovirus, either as a single infection or coinfection, illustrating persistent co-circulation of some respiratory viruses despite active infection control measures.

5.
Lancet Infect Dis ; 22(6): 754-756, 2022 06.
Article in English | MEDLINE | ID: covidwho-1864664
6.
Clin Infect Dis ; 2021 Nov 23.
Article in English | MEDLINE | ID: covidwho-1621585

ABSTRACT

BACKGROUND: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectious virus isolation in outpatients with coronavirus disease 2019 (COVID-19) has been associated with viral RNA levels and symptom duration, little is known about the host, disease, and viral determinants of infectious virus detection. METHODS: COVID-19 adult outpatients were enrolled within 7 days of symptom onset. Clinical symptoms were recorded via patient diary. Nasopharyngeal swabs were collected to quantitate SARS-CoV-2 RNA by reverse transcriptase polymerase chain reaction and for infectious virus isolation in Vero E6-cells. SARS-CoV-2 antibodies were measured in serum using a validated ELISA assay. RESULTS: Among 204 participants with mild-to-moderate symptomatic COVID-19, the median nasopharyngeal viral RNA was 6.5 (interquartile range [IQR] 4.7-7.6 log10 copies/mL), and 26% had detectable SARS-CoV-2 antibodies (immunoglobulin (Ig)A, IgM, IgG, and/or total Ig) at baseline. Infectious virus was recovered in 7% of participants with SARS-CoV-2 antibodies compared to 58% of participants without antibodies (prevalence ratio [PR] = 0.12, 95% confidence interval [CI]: .04, .36; P = .00016). Infectious virus isolation was also associated with higher levels of viral RNA (mean RNA difference +2.6 log10, 95% CI: 2.2, 3.0; P < .0001) and fewer days since symptom onset (PR = 0.79, 95% CI: .71, .88 per day; P < .0001). CONCLUSIONS: The presence of SARS-CoV-2 antibodies is strongly associated with clearance of infectious virus. Seropositivity and viral RNA levels are likely more reliable markers of infectious virus clearance than subjective measure of COVID-19 symptom duration. Virus-targeted treatment and prevention strategies should be administered as early as possible and ideally before seroconversion. CLINICAL TRIALS REGISTRATION: NCT04405570.

7.
Open Forum Infect Dis ; 9(1): ofab498, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1606723

ABSTRACT

BACKGROUND: The objective of this study was to characterize hospitalized coronavirus disease 2019 (COVID-19) patients and describe their real-world treatment patterns and outcomes over time. METHODS: Adult patients hospitalized on May 1, 2020-December 31, 2020 with a discharge diagnosis of COVID-19 were identified from the Premier Healthcare Database. Patient and hospital characteristics, treatments, baseline severity based on oxygen support, length of stay (LOS), intensive care unit (ICU) utilization, and mortality were examined. RESULTS: The study included 295657 patients (847 hospitals), with median age of 66 (interquartile range, 54-77) years. Among each set of demographic comparators, the majority were male, white, and over 65. Approximately 85% had no supplemental oxygen charges (NSOc) or low-flow oxygen (LFO) at baseline, whereas 75% received no more than NSOc or LFO as maximal oxygen support at any time during hospitalization. Remdesivir (RDV) and corticosteroid treatment utilization increased over time. By December, 50% were receiving RDV and 80% were receiving corticosteroids. A higher proportion initiated COVID-19 treatments within 2 days of hospitalization in December versus May (RDV, 87% vs 40%; corticosteroids, 93% vs 62%; convalescent plasma, 68% vs 26%). There was a shift toward initiating RDV in patients on NSOc or LFO (68.0% [May] vs 83.1% [December]). Median LOS decreased over time. Overall mortality was 13.5% and it was highest for severe patients (invasive mechanical ventilation/extracorporeal membrane oxygenation [IMV/ECMO], 53.7%; high-flow oxygen/noninvasive ventilation [HFO/NIV], 32.2%; LFO, 11.7%; NSOc, 7.3%). The ICU use decreased, whereas mortality decreased for NSOc and LFO. CONCLUSIONS: Clinical management of COVID-19 is rapidly evolving. This large observational study found that use of evidence-based treatments increased from May to December 2020, whereas improvement in outcomes occurred over this time-period.

8.
Sci Transl Med ; 14(628): eabl7430, 2022 Jan 19.
Article in English | MEDLINE | ID: covidwho-1593318

ABSTRACT

There is an urgent need for an effective, oral, direct-acting therapeutic to block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent progression to severe coronavirus disease 2019 (COVID-19). In a phase 2a double-blind, placebo-controlled, randomized, multicenter clinical trial, we evaluated the safety, tolerability, and antiviral efficacy of the nucleoside analog molnupiravir in 202 unvaccinated participants with confirmed SARS-CoV-2 infection and symptom duration <7 days. Participants were randomized 1:1 to receive molnupiravir (200 mg) or placebo and then 3:1 to receive molnupiravir (400 or 800 mg) or placebo, orally twice daily for 5 days. Antiviral activity was assessed by reverse transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 RNA in nasopharyngeal swabs. Infectious virus was assessed by inoculation of cultured Vero cells with samples from nasopharyngeal swabs and was detected by RT-PCR. Time to viral RNA clearance (primary endpoint) was decreased in the 800-mg molnupiravir group (median 14 days) compared to the placebo group (median 15 days) (log rank P value = 0.013). Of participants receiving 800 mg of molnupiravir, 92.5% achieved viral RNA clearance compared with 80.3% of placebo recipients by study end (4 weeks). Infectious virus (secondary endpoint) was detected in swabs from 1.9% of the 800-mg molnupiravir group compared with 16.7% of the placebo group at day 3 of treatment (P = 0.016). At day 5 of treatment, infectious virus was not isolated from any participants receiving 400 or 800 mg of molnupiravir compared with 11.1% of placebo recipients (P = 0.034 and 0.027, respectively). Molnupiravir was well tolerated across all doses.


Subject(s)
COVID-19 , Animals , Chlorocebus aethiops , Cytidine/analogs & derivatives , Humans , Hydroxylamines , RNA, Viral/genetics , SARS-CoV-2 , Treatment Outcome , Vero Cells
9.
PLoS One ; 16(12): e0260879, 2021.
Article in English | MEDLINE | ID: covidwho-1566553

ABSTRACT

INTRODUCTION: Symptoms associated with SARS-CoV-2 infection remain incompletely understood, especially among ambulatory, non-hospitalized individuals. With host factors, symptoms predictive of SARS-CoV-2 could be used to guide testing and intervention strategies. METHODS: Between March 16 and September 3, 2020, we examined the characteristics and symptoms reported by individuals presenting to a large outpatient testing program in the Southeastern US for nasopharyngeal SARS-CoV-2 RNA RT-PCR testing. Using self-reported symptoms, demographic characteristics, and exposure and travel histories, we identified the variables associated with testing positive using modified Poisson regression. RESULTS: Among 20,177 tested individuals, the proportion positive was 9.4% (95% CI, 9.0-9.8) and was higher for men, younger individuals, and racial/ethnic minorities (all P<0.05); the positivity proportion was higher for Hispanics (26.9%; 95% CI. 24.9-29.0) compared to Blacks (8.6%; 95% CI, 7.6-9.7) or Whites (5.8%; 95% CI, 5.4-6.3). Individuals reporting contact with a COVID-19 case had the highest positivity proportion (22.8%; 95% CI, 21.5-24.1). Among the subset of 8,522 symptomatic adults who presented for testing after May 1, when complete symptom assessments were performed, SARS-CoV-2 RNA PCR was detected in 1,116 (13.1%). Of the reported symptoms, loss of taste or smell was most strongly associated with SARS-CoV-2 RNA detection with an adjusted risk ratio of 3.88 (95% CI, 3.46-4.35). The presence of chills, fever, cough, aches, headache, fatigue and nasal congestion also significantly increased the risk of detecting SARS-CoV-2 RNA, while diarrhea or nausea/vomiting, although not uncommon, were significantly more common in those with a negative test result. Symptom combinations were frequent with 67.9% experiencing ≥4 symptoms, including 19.8% with ≥8 symptoms; report of greater than three symptoms increased the risk of SARS-CoV-2 RNA detection. CONCLUSIONS: In a large outpatient population in the Southeastern US, several symptoms, most notably loss of taste or smell, and greater symptom burden were associated with detection of SARS-CoV-2 RNA. Persons of color and those with who were a contact of a COVID-19 case were also more likely to test positive. These findings suggest that, given limited SARS-CoV-2 testing capacity, symptom presentation and host characteristics can be used to guide testing and intervention prioritization.


Subject(s)
COVID-19 Testing , COVID-19/diagnosis , COVID-19/virology , Outpatients , SARS-CoV-2/physiology , Adolescent , Adult , Female , Humans , Male , Middle Aged , RNA, Viral/genetics , Young Adult
10.
Clin Infect Dis ; 73(9): 1717-1721, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1501059

ABSTRACT

As of March 2021, coronavirus disease 2019 (COVID-19) had caused more than 123 million infections and almost 3 million deaths worldwide. Dramatic advances have been made in vaccine development and nonpharmaceutical interventions to stop the spread of infection. However, treatments to stop disease progression are limited. A wide variety of "repurposed" drugs evaluated for treatment of COVID-19 have had little or no benefit. More recently, intravenous monoclonal antibody (mAb) combinations have been authorized by the US Food and Drug Administration for emergency use for outpatients with mild to moderate COVID-19 including some active against emerging severe acute respiratory syndrome coronavirus 2 variants of concern. Easier to administer therapeutics including intramuscular and subcutaneous mAbs and oral antivirals are in clinical trials. Reliable, safe, effective COVID-19 treatment for early infection in the outpatient setting is of urgent and critical importance. Availability of such treatment should lead to reduced progression of COVID-19.


Subject(s)
COVID-19 , Pharmaceutical Preparations , COVID-19/drug therapy , Humans , Outpatients , SARS-CoV-2
11.
Clin Infect Dis ; 2021 Oct 01.
Article in English | MEDLINE | ID: covidwho-1447582

ABSTRACT

BACKGROUND: Remdesivir (RDV) improved clinical outcomes among hospitalized COVID-19 patients in randomized trials, but data from clinical practice are limited. METHODS: We examined survival outcomes for US patients hospitalized with COVID-19 between Aug-Nov 2020 and treated with RDV within two-days of hospitalization vs. those not receiving RDV during their hospitalization using the Premier Healthcare Database. Preferential within-hospital propensity score matching with replacement was used. Additionally, patients were also matched on baseline oxygenation level (no supplemental oxygen charges (NSO), low-flow oxygen (LFO), high-flow oxygen/non-invasive ventilation (HFO/NIV) and invasive mechanical ventilation/ECMO (IMV/ECMO) and two-month admission window and excluded if discharged within 3-days of admission (to exclude anticipated discharges/transfers within 72-hrs consistent with ACTT-1 study). Cox Proportional Hazards models were used to assess time to 14-/28-day mortality overall and for patients on NSO, LFO, HFO/NIV and IMV/ECMO. RESULTS: 28,855 RDV patients were matched to 16,687 unique non-RDV patients. Overall, 10.6% and 15.4% RDV patients died within 14- and 28-days, respectively compared with 15.4% and 19.1% non-RDV patients. Overall, RDV was associated with a reduction in mortality at 14-days (HR[95% CI]: 0.76[0.70-0.83]) and 28-days (0.89[0.82-0.96]). This mortality benefit was also seen for NSO, LFO and IMV/ECMO at 14-days (NSO:0.69[0.57-0.83], LFO:0.68[0.80-0.77], IMV/ECMO:0.70[0.58-0.84]) and 28-days (NSO:0.80[0.68-0.94], LFO:0.77[0.68-0.86], IMV/ECMO:0.81[0.69-0.94]). Additionally, HFO/NIV RDV group had a lower risk of mortality at 14-days (0.81[0.70-0.93]) but no statistical significance at 28-days. CONCLUSIONS: RDV initiated upon hospital admission was associated with improved survival among COVID-19 patients. Our findings complement ACTT-1 and support RDV as a foundational treatment for hospitalized COVID-19 patients.

12.
J Crohns Colitis ; 14(14 Suppl 3): S769-S773, 2020 Oct 21.
Article in English | MEDLINE | ID: covidwho-883091

ABSTRACT

Patients with inflammatory bowel diseases [IBD] are frequently treated with immunosuppressant medications. During the coronavirus disease 2019 [COVID-19] pandemic, recommendations for IBD management have included that patients should stay on their immunosuppressant medications if they are not infected with the severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], but to temporarily hold these medications if symptomatic with COVID-19 or asymptomatic but have tested positive for SARS-CoV-2. As more IBD patients are infected globally, it is important to also understand how to manage IBD medications during convalescence while an individual with IBD is recovering from COVID-19. In this review, we address the differences between a test-based versus a symptoms-based strategy as related to COVID-19, and offer recommendations on when it is appropriate to consider restarting IBD therapy in patients testing positive for SARS-CoV-2 or with clinical symptoms consistent with COVID-19. In general, we recommend a symptoms-based approach, due to the current lack of confidence in the accuracy of available testing and the clinical significance of prolonged detection of virus via molecular testing.


Subject(s)
Betacoronavirus , Clinical Laboratory Techniques , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Immunocompromised Host , Immunosuppressive Agents/administration & dosage , Inflammatory Bowel Diseases/drug therapy , Pandemics/prevention & control , Pneumonia, Viral/immunology , Pneumonia, Viral/prevention & control , Asymptomatic Infections , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , Coronavirus Infections/diagnosis , Drug Administration Schedule , Humans , Immunosuppressive Agents/therapeutic use , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/immunology , Pneumonia, Viral/diagnosis , Risk Assessment , SARS-CoV-2
13.
Influenza Other Respir Viruses ; 14(4): 465-469, 2020 07.
Article in English | MEDLINE | ID: covidwho-602683

ABSTRACT

This study was conducted to determine the prevalence of respiratory viral infections (RVI) in persons living with HIV (PLH) admitted with a respiratory complaint using real-time reverse transcription polymerase chain reaction and primer-independent next-generation sequencing (NGS). Of 82 subjects, respiratory viruses were the most common pathogen identified in 27 (33%), followed by fungus and bacteria in 8 (10%) and 4 (5%) subjects, respectively. Among subjects with RVI, 11 (41%) required ICU admission and 16 (59%) required mechanical ventilation. The proportion of respiratory viruses identified, and the associated complicated hospital course highlights the significant role that RVIs play in the lung health of PLH.


Subject(s)
HIV Infections/epidemiology , HIV Infections/virology , High-Throughput Nucleotide Sequencing , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Viruses/genetics , Cost of Illness , Female , HIV/genetics , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Pneumonia, Viral/epidemiology , Prevalence , Prospective Studies , Respiratory Tract Infections/complications , Tertiary Care Centers/statistics & numerical data , Viruses/classification , Viruses/isolation & purification , Viruses/pathogenicity
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