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1.
J Korean Med Sci ; 37(29): e238, 2022 Jul 25.
Article in English | MEDLINE | ID: covidwho-1963382

ABSTRACT

Despite the low prevalence of secondary bacterial infection in coronavirus disease 2019 (COVID-19) patients, most of them were administered antibiotic therapy empirically. However, the prognostic impact of empirical antibiotic therapy has not been evaluated. We conducted retrospective propensity score-matched case-control study of 233 COVID-19 patients with moderate to severe illnesses who required oxygen therapy and evaluated whether empirical antibiotic therapy could improve clinical outcomes. Empirical antibiotic therapy did not improve clinical outcomes including length of stay, days with oxygen requirement, the proportion of patients with increased oxygen demand, the proportion of patients who required mechanical ventilation, and overall mortality. This finding implies that routine administration of antibiotics for the treatment of COVID-19 is not essential and should be restricted.


Subject(s)
COVID-19 , Anti-Bacterial Agents/therapeutic use , Case-Control Studies , Humans , Oxygen/therapeutic use , Retrospective Studies
2.
Virulence ; 13(1): 1242-1251, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1956537

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern have been emerging. However, knowledge of temporal and spatial dynamics of SARS-CoV-2 is limited. This study characterized SARS-CoV-2 evolution in immunosuppressed patients with long-term SARS-CoV-2 shedding for 73-250 days, without specific treatment. We conducted whole-genome sequencing of 27 serial samples, including 26 serial samples collected from various anatomic sites of two patients and the first positive sample from patient 2's mother. We analysed the intrahost temporal dynamics and genomic diversity of the viral population within different sample types. Intrahost variants emerging during infection showed diversity between individual hosts. Remarkably, N501Y, P681R, and E484K, key substitutions within spike protein, emerged in vivo during infection and became the dominant population. P681R, which had not yet been detected in the publicly available genome in Korea, appeared within patient 1 during infection. Mutually exclusive substitutions at residues R346 (R346S and R346I) and E484 (E484K and E484A) of spike protein and continuous turnover of these substitutions occurred. Unique genetic changes were observed in urine samples. A household transmission from patient 2 to his mother, at least 38 days after the diagnosis, was characterized. Viruses may differently mutate and adjust to the host selective pressure, which could enable the virus to replicate efficiently for fitness in each host. Intrahost variants could be candidate variants likely to spread to the population eventually. Our findings may provide new insights into the dynamics of SARS-CoV-2 in response to interactions between the virus and host.


Subject(s)
COVID-19 , Immunocompromised Host , SARS-CoV-2 , Virus Shedding , COVID-19/transmission , Humans , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Whole Genome Sequencing
4.
BMC Med ; 20(1): 181, 2022 05 04.
Article in English | MEDLINE | ID: covidwho-1892212

ABSTRACT

BACKGROUND: Practical guidance is needed regarding the vaccination of coronavirus disease 2019 (COVID-19) convalescent individuals in resource-limited countries. It includes the number of vaccine doses that should be given to unvaccinated patients who experienced COVID-19 early in the pandemic. METHODS: We recruited COVID-19 convalescent individuals who received one or two doses of an mRNA vaccine within 6 or around 18 months after a diagnosis of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Their samples were assessed for IgG-binding or neutralizing activity and cell-mediated immune responses against SARS-CoV-2 wild-type and variants of concern. RESULTS: A total of 43 COVID-19 convalescent individuals were analyzed in the present study. The results showed that humoral and cellular immune responses against SARS-CoV-2 wild-type and variants of concern, including the Omicron variant, were comparable among patients vaccinated within 6 versus around 18 months. A second dose of vaccine did not significantly increase immune responses. CONCLUSION: One dose of mRNA vaccine should be considered sufficient to elicit a broad immune response even around 18 months after a COVID-19 diagnosis.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Testing , COVID-19 Vaccines , Humans , Immunity, Cellular , RNA, Messenger/genetics , SARS-CoV-2/genetics , Vaccination , Vaccines, Synthetic , mRNA Vaccines
6.
Lancet Respir Med ; 2022 May 23.
Article in English | MEDLINE | ID: covidwho-1864689

ABSTRACT

BACKGROUND: Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19. METHODS: In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168. FINDINGS: Between Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012). INTERPRETATION: In hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered. FUNDING: National Institute of Allergy and Infectious Diseases.

7.
J Infect Dis ; 2022 Mar 17.
Article in English | MEDLINE | ID: covidwho-1816122

ABSTRACT

BACKGROUND: Humoral immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may wane rapidly in persons recovered from mild coronavirus disease 2019 (COVID-19), but little is known about the longevity. METHODS: Serum samples were obtained 8, 12, and 18 months after infection from 20 patients with mild COVID-19. The binding activities of serum antibodies (IgA, IgG, and IgM) against SARS-CoV-2 antigens of the Wuhan-1 reference strain (wild-type) and the B.1.1.7, P.1, B.1.167.2, and B.1.1.529 variants were measured by enzyme-linked immunosorbent assays. Neutralizing antibody titers were measured using a cytopathic effect-based live virus neutralization assay. RESULTS: Serum IgA and IgG antibodies against spike or receptor-binding domain (RBD) protein of wild-type SARS-CoV-2 were detected for up to 18 months, and neutralizing antibodies persisted for 8 to 18 months after infection. However, any significant antibody responses against RBD proteins of SARS-CoV-2 variants were not observed, and median neutralizing antibody titers against the Delta variant at 8, 12, and 18 months were 8-11 fold lower than against wild-type viruses (P < .001). CONCLUSIONS: Humoral immunity persisted for up to 18 months after SARS-CoV-2 infection in patients with mild COVID-19. Humoral immune activity against more recently circulating variants, however, was reduced in this population.

8.
J Korean Med Sci ; 37(16): e126, 2022 Apr 25.
Article in English | MEDLINE | ID: covidwho-1809347

ABSTRACT

BACKGROUND: The relationship between changes in anxiety levels and personal protective equipment (PPE) use is yet to be evaluated. The present study assessed this relationship among healthcare workers (HCWs) involved in the care of patients with coronavirus disease 2019 (COVID-19). METHODS: An online survey was conducted in a municipal hospital with 195 nationally designated negative pressure isolation units in Korea. Anxiety level was measured using the self-rating anxiety scale (SAS), and changes in anxiety levels were assessed based on the time when COVID-19 vaccine was introduced in March 2021 in Korea. Monthly PPE usage between June 2020 and May 2021 was investigated. RESULTS: The mean SAS score (33.25 ± 5.97) was within normal range and was lower than those reported in previous studies conducted before COVID-19 vaccination became available. Among the 93 HCWs who participated, 64 (68.8%) answered that their fear of contracting COVID-19 decreased after vaccination. The number of coveralls used per patient decreased from 33.6 to 0. However, a demand for more PPE than necessary was observed in situations where HCWs were exposed to body fluids and secretions (n = 38, 40.9%). Excessive demand for PPE was not related to age, working experience, or SAS score. CONCLUSION: Anxiety in HCWs exposed to COVID-19 was lower than it was during the early period of the pandemic, and the period before vaccination was introduced. The number of coveralls used per patient also decreased although an excessive demand for PPE was observed.


Subject(s)
COVID-19 , Personal Protective Equipment , Anxiety/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Health Personnel , Humans , SARS-CoV-2
9.
Front Immunol ; 13: 830433, 2022.
Article in English | MEDLINE | ID: covidwho-1785337

ABSTRACT

Background: Despite the fact of ongoing worldwide vaccination programs for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), understanding longevity, breadth, and type of immune response to coronavirus disease-19 (COVID-19) is still important to optimize the vaccination strategy and estimate the risk of reinfection. Therefore, we performed thorough immunological assessments 1 year post-COVID-19 with different severity. Methods: We analyzed peripheral blood mononuclear cells and plasma samples at 1 year post-COVID-19 in patients who experienced asymptomatic, mild, and severe illness to assess titers of various isotypes of antibodies (Abs) against SARS-CoV-2 antigens, phagocytic capability, and memory B- and T-cell responses. Findings: A total of 24 patients (7, 9, and 8 asymptomatic, mild, and severe patients, respectively) and eight healthy volunteers were included in this study. We firstly showed that disease severity is correlated with parameters of immune responses at 1 year post-COVID-19 that play an important role in protecting against reinfection with SARS-CoV-2, namely, the phagocytic capacity of Abs and memory B-cell responses. Interpretation: Various immune responses at 1 year post-COVID-19, particularly the phagocytic capacity and memory B-cell responses, were dependent on the severity of the prior COVID-19. Our data could provide a clue for a tailored vaccination strategy after natural infection according to the severity of COVID-19.


Subject(s)
COVID-19 , Antibodies, Viral , Humans , Immunity , Leukocytes, Mononuclear , Reinfection , SARS-CoV-2 , Severity of Illness Index
10.
J Korean Med Sci ; 37(9): e70, 2022 Mar 07.
Article in English | MEDLINE | ID: covidwho-1731751

ABSTRACT

Concerns about the effectiveness of current vaccines against the rapidly spreading severe acute respiratory syndrome-coronavirus-2 omicron (B.1.1.529) variant are increasing. This study aimed to assess neutralizing antibody activity against the wild-type (BetaCoV/Korea/KCDC03/2020), delta, and omicron variants after full primary and booster vaccinations with BNT162b2. A plaque reduction neutralization test was employed to determine 50% neutralizing dilution (ND50) titers in serum samples. ND50 titers against the omicron variant (median [interquartile range], 5.3 [< 5.0-12.7]) after full primary vaccination were lower than those against the wild-type (144.8 [44.7-294.0]) and delta (24.3 [14.3-81.1]) variants. Furthermore, 19/30 participants (63.3%) displayed lower ND50 titers than the detection threshold (< 10.0) against omicron after full primary vaccination. However, the booster vaccine significantly increased ND50 titers against BetaCoV/Korea/KCDC03/2020, delta, and omicron, although titers against omicron remained lower than those against the other variants (P < 0.001). Our study suggests that booster vaccination with BNT162b2 significantly increases humoral immunity against the omicron variant.


Subject(s)
Antibodies, Neutralizing , COVID-19 , Adult , Aged , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , SARS-CoV-2 , Vaccination
12.
J Korean Med Sci ; 37(8): e67, 2022 Feb 28.
Article in English | MEDLINE | ID: covidwho-1714984

ABSTRACT

We investigated the kinetics of the neutralizing antibody responses to the severe acute respiratory syndrome-coronavirus-2 delta variant over the course of 1 year in 16 patients infected at the beginning of the pandemic. In patients with severe disease, neutralizing responses to the delta variant were detectable, albeit at lower levels than responses to the wild type. Neutralizing responses to the delta variant were undetectable, however, in asymptomatic persons. This finding implies that the vaccination strategy for persons with past natural infection should depend on the severity of the previous infection.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/immunology , SARS-CoV-2/immunology , Adult , Aged , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Female , Humans , Kinetics , Male , Middle Aged , Severity of Illness Index , Vaccination , Young Adult
13.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315037

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the current COVID-19 global pandemic. Vaccines and therapeutics are urgently needed for this highly transmissible virus. In this study, we screened human monoclonal antibodies (mAbs) targeting the receptor binding domain (RBD) of the SARS-CoV-2 spike protein from an antibody library constructed from peripheral blood mononuclear cells of a COVID-19 convalescent patient. A potent neutralizing antibody, termed CT-P59, was identified and found to be effective against various SARS-CoV-2 isolates including the D614G spike protein variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/SARS-CoV-2 RBD showed that CT-P59 blocks interaction regions of SARS-CoV-2 RBD for its cellular receptor, angiotensin converting enzyme 2 (ACE2). The binding orientation of CT-P59 is notably different from the previously reported neutralizing mAbs targeting SARS-CoV-2 RBD suggesting that CT-P59 can be a novel binder to SARS-CoV-2 RBD. Therapeutic effects of CT-P59 were evaluated in three animal models (ferret, hamster, and rhesus monkey), and a substantial reduction in viral titre along with alleviation of clinical symptoms was observed. These findings suggest that the human monoclonal antibody, CT-P59, is a promising therapeutic candidate for treatment of COVID-19.

14.
Emerg Infect Dis ; 28(2): 347-353, 2022 02.
Article in English | MEDLINE | ID: covidwho-1648662

ABSTRACT

We conducted a retrospective cohort study using claims data to determine the number and types of complications from coronavirus disease (COVID-19) that patients experience and which patients are more vulnerable to those complications compared with complications in patients with influenza. Among the cohort, 19.6% of COVID-19 patients and 28.5% of influenza patients had >1 new complication. In most complications, COVID-19 patients had lower or similar relative risk compared with influenza patients; exceptions were hair loss, heart failure, mood disorder, and dementia. Young to middle-aged adult COVID-19 patients and patients in COVID-19 hotspots had a higher risk for complications. Overall, COVID-19 patients had fewer complications than influenza patients, but caution is necessary in high-risk groups. If the fatality rate for COVID-19 is reduced through vaccination, management strategies for this disease could be adapted, similar to those for influenza management, such as easing restrictions on economic activity or requirements for close-contact isolation.


Subject(s)
COVID-19 , Influenza, Human , Adult , Humans , Influenza, Human/complications , Influenza, Human/epidemiology , Middle Aged , Retrospective Studies , SARS-CoV-2 , Seasons
15.
Infect Chemother ; 53(4): 776-785, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1607076

ABSTRACT

BACKGROUND: Co-infection with bacteria and severe acute respiratory syndrome coronavirus 2 may result in greater use of healthcare resources and a poor prognosis. Therefore, early selection and use of optimal antibiotics are essential. The direct rapid antibiotic susceptibility test (dRAST) can detect antibiotic resistance within 6 h of a Gram smear result. This study aimed to assess the effectiveness of dRAST for improving early selection of appropriate antibiotics for coronavirus disease 2019 (COVID-19) patients with bacteremia. MATERIALS AND METHODS: This retrospective study included 96 blood culture-positive COVID-19 patients. Bacterial isolates and antimicrobial resistance profiles of each case were evaluated. Cases were divided into two groups based on whether they underwent conventional antibiotic susceptibility test (AST) or dRAST. The time to optimal targeted treatment for the two groups was investigated and compared. In addition, we examined the proportion of cases for which appropriate antibiotics were selected and broad spectrum antibiotics were administered at 72 h from blood sample collection. RESULTS: The mean time to optimal targeted antibiotic treatment was shorter for the dRAST group [55.7; standard deviation (SD), 28.7 vs. 92.3; SD, 51.1 h; P = 0.041]. The proportion of cases receiving optimal targeted antibiotics 72 h after blood collection for culture was higher [6/10 (60.0%) vs. 10/25 (40.0%)] and the percentage receiving broad spectrum antibiotics at 72 h was lower [6/10 (60.0%) vs. 19/25 (76.0%)] in the dRAST group than in the conventional AST group. In terms of microbiology profile, the contamination rate was high (35.5%) and multidrug-resistant strains were common (63.2%) in COVID-19 patients with bacteremia. CONCLUSION: Application of dRAST for selection of antibiotics to treat bacteremia in COVID-19 patients may enable earlier and optimal treatment. The high incidence of contamination and resistant organisms in blood cultures from COVID-19 patients suggest that dRAST may speed up appropriate targeted treatment.

16.
Emerg Infect Dis ; 27(12): 3052-3062, 2021 12.
Article in English | MEDLINE | ID: covidwho-1528794

ABSTRACT

Middle East respiratory syndrome coronavirus (MERS-CoV) infects humans and dromedary camels and is responsible for an ongoing outbreak of severe respiratory illness in humans in the Middle East. Although some mutations found in camel-derived MERS-CoV strains have been characterized, most natural variation found across MERS-CoV isolates remains unstudied. We report on the environmental stability, replication kinetics, and pathogenicity of several diverse isolates of MERS-CoV, as well as isolates of severe acute respiratory syndrome coronavirus 2, to serve as a basis of comparison with other stability studies. Although most MERS-CoV isolates had similar stability and pathogenicity in our experiments, the camel-derived isolate C/KSA/13 had reduced surface stability, and another camel isolate, C/BF/15, had reduced pathogenicity in a small animal model. These results suggest that although betacoronaviruses might have similar environmental stability profiles, individual variation can influence this phenotype, underscoring the need for continual global viral surveillance.


Subject(s)
COVID-19 , Middle East Respiratory Syndrome Coronavirus , Aerosols , Animals , Camelus , Humans , Middle East Respiratory Syndrome Coronavirus/genetics , SARS-CoV-2 , Virulence , Zoonoses
17.
Clin Transl Sci ; 15(3): 732-740, 2022 03.
Article in English | MEDLINE | ID: covidwho-1526361

ABSTRACT

Remdesivir, an antiviral agent for the treatment of coronavirus disease 2019 (COVID-19), is metabolized intracellularly, with these metabolites eliminated predominantly in urine. Because of a lack of safety and pharmacokinetic (PK) data, remdesivir is not currently recommended for patients with estimated glomerular filtration rate less than 30 ml/min/1.73 m2 and those on hemodialysis. This study evaluated the PKs of remdesivir and its metabolite, GS-441524, in patients with COVID-19 who were and were not receiving renal replacement therapy (RRT). This study enrolled two patients with normal renal function, two with impaired renal function not receiving RRT, two receiving continuous RRT (CRRT), and three undergoing intermittent hemodialysis (IHD). Patients were administered 200 mg remdesivir on the first day, followed by 100 mg/day for 5-10 days. Serial blood samples were collected for PK analysis, and PK parameters were assessed by a noncompartmental method. Systemic exposure to remdesivir was higher in patients with impaired renal function and those receiving CRRT than in patients with normal renal function, but was similar in patients undergoing IHD and those with normal renal function. By contrast, systemic exposure to GS-441524 was highest in patients undergoing IHD, followed by patients with impaired renal function and those receiving CRRT, and lowest in patients with normal renal function. The PK profiles of remdesivir and GS-441524 varied according to renal function and RRT. The impact of PK changes of remdesivir and its metabolite on safety and efficacy should be considered when administering remdesivir to patients with COVID-19 with renal impairment.


Subject(s)
COVID-19 , Adenosine/analogs & derivatives , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , COVID-19/drug therapy , Humans , Kidney/metabolism , Renal Replacement Therapy/methods
18.
Lancet Respir Med ; 9(12): 1365-1376, 2021 12.
Article in English | MEDLINE | ID: covidwho-1472211

ABSTRACT

BACKGROUND: Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19. METHODS: We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA). Eligible patients were hospitalised adults (aged ≥18 years) with SARS-CoV-2 infection, as confirmed by a positive RT-PCR test, and who met one of the following criteria suggestive of lower respiratory tract infection: the presence of radiographic infiltrates on imaging, a peripheral oxygen saturation on room air of 94% or less, or requiring supplemental oxygen. Patients were excluded if they had either an alanine aminotransferase or an aspartate aminotransferase concentration more than five times the upper limit of normal; had impaired renal function; were allergic to the study product; were pregnant or breast feeding; were already on mechanical ventilation; or were anticipating discharge from the hospital or transfer to another hospital within 72 h of enrolment. Patients were randomly assigned (1:1) to receive intravenous remdesivir as a 200 mg loading dose on day 1 followed by a 100 mg maintenance dose administered daily for up to 9 days and up to four doses of either 44 µg interferon beta-1a (interferon beta-1a group plus remdesivir group) or placebo (placebo plus remdesivir group) administered subcutaneously every other day. Randomisation was stratified by study site and disease severity at enrolment. Patients, investigators, and site staff were masked to interferon beta-1a and placebo treatment; remdesivir treatment was given to all patients without masking. The primary outcome was time to recovery, defined as the first day that a patient attained a category 1, 2, or 3 score on the eight-category ordinal scale within 28 days, assessed in the modified intention-to-treat population, defined as all randomised patients who were classified according to actual clinical severity. Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04492475. FINDINGS: Between Aug 5, 2020, and Nov 11, 2020, 969 patients were enrolled and randomly assigned to the interferon beta-1a plus remdesivir group (n=487) or to the placebo plus remdesivir group (n=482). The mean duration of symptoms before enrolment was 8·7 days (SD 4·4) in the interferon beta-1a plus remdesivir group and 8·5 days (SD 4·3) days in the placebo plus remdesivir group. Patients in both groups had a time to recovery of 5 days (95% CI not estimable) (rate ratio of interferon beta-1a plus remdesivir group vs placebo plus remdesivir 0·99 [95% CI 0·87-1·13]; p=0·88). The Kaplan-Meier estimate of mortality at 28 days was 5% (95% CI 3-7%) in the interferon beta-1a plus remdesivir group and 3% (2-6%) in the placebo plus remdesivir group (hazard ratio 1·33 [95% CI 0·69-2·55]; p=0·39). Patients who did not require high-flow oxygen at baseline were more likely to have at least one related adverse event in the interferon beta-1a plus remdesivir group (33 [7%] of 442 patients) than in the placebo plus remdesivir group (15 [3%] of 435). In patients who required high-flow oxygen at baseline, 24 (69%) of 35 had an adverse event and 21 (60%) had a serious adverse event in the interferon beta-1a plus remdesivir group compared with 13 (39%) of 33 who had an adverse event and eight (24%) who had a serious adverse event in the placebo plus remdesivir group. INTERPRETATION: Interferon beta-1a plus remdesivir was not superior to remdesivir alone in hospitalised patients with COVID-19 pneumonia. Patients who required high-flow oxygen at baseline had worse outcomes after treatment with interferon beta-1a compared with those given placebo. FUNDING: The National Institute of Allergy and Infectious Diseases (USA).


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19 , Interferon beta-1a/therapeutic use , Adenosine Monophosphate/therapeutic use , Adult , Aged , Alanine/therapeutic use , COVID-19/drug therapy , Double-Blind Method , Female , Humans , Japan , Male , Mexico , Middle Aged , Oxygen , Republic of Korea , SARS-CoV-2 , Singapore , Treatment Outcome , United States
19.
Nat Commun ; 12(1): 5975, 2021 10 13.
Article in English | MEDLINE | ID: covidwho-1467103

ABSTRACT

Acquired somatic mutations in hematopoietic stem and progenitor cells (clonal hematopoiesis or CH) are associated with advanced age, increased risk of cardiovascular and malignant diseases, and decreased overall survival. These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH. A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19. Whether CH predisposes to severe Covid-19 or other infections is unknown. Among 525 individuals with Covid-19 from Memorial Sloan Kettering (MSK) and the Korean Clonal Hematopoiesis (KoCH) consortia, we show that CH is associated with severe Covid-19 outcomes (OR = 1.85, 95%=1.15-2.99, p = 0.01), in particular CH characterized by non-cancer driver mutations (OR = 2.01, 95% CI = 1.15-3.50, p = 0.01). We further explore the relationship between CH and risk of other infections in 14,211 solid tumor patients at MSK. CH is significantly associated with risk of Clostridium Difficile (HR = 2.01, 95% CI: 1.22-3.30, p = 6×10-3) and Streptococcus/Enterococcus infections (HR = 1.56, 95% CI = 1.15-2.13, p = 5×10-3). These findings suggest a relationship between CH and risk of severe infections that warrants further investigation.


Subject(s)
COVID-19/etiology , COVID-19/pathology , Clonal Hematopoiesis/genetics , Hematopoietic Stem Cells/virology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/immunology , Child , Child, Preschool , Clonal Hematopoiesis/immunology , Cohort Studies , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Mutation/immunology , Neoplasms/genetics , Risk Factors , SARS-CoV-2 , Severity of Illness Index
20.
J Korean Med Sci ; 36(38): e274, 2021 Oct 04.
Article in English | MEDLINE | ID: covidwho-1450798

ABSTRACT

Applying work restrictions for asymptomatic healthcare personnel (HCP) with potential exposure to coronavirus disease 2019 (COVID-19) is recommended to prevent transmission from potentially contagious HCP to patients and other HCP. However, it can lead to understaffing, which threatens the safety of both patients and HCP. We evaluated 203 COVID-19 exposure events at a single tertiary hospital from January 2020 to June 2021. A total of 2,365 HCP were potentially exposed, and work restrictions were imposed on 320 HCP, leading to the loss of 3,311 working days. However, only one of the work-restricted HCP was confirmed with COVID-19. During the study period, the work restriction measures might be taken excessively compared to their benefit, so establishing more effective standards for work restriction is required.


Subject(s)
COVID-19/prevention & control , COVID-19/transmission , Health Personnel , Occupational Exposure/prevention & control , Occupational Health , Primary Prevention/methods , Humans , Republic of Korea , Retrospective Studies , SARS-CoV-2 , Workplace
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