Journal Watch

27/03/2024

epidemiológica de incremento de casos de por Semana Santa!!!

¿Por qué?

1⃣En el año 2023, la gran movilización de susceptibles a zonas calientes de dengue durante la semana santa sirvió de gatillo para el incremento de casos de dengue en todo el Perú entre la semana 12 y el pico que se registró en la semana 20.

2⃣Lo grave de la situación es que, mientras que en la semana 11 del 2023 el Perú se reportaron 2842 casos y en la semana 20, 19268 casos (x6,78), este 2024 en la semana 11 se reportaron >14000 casos, por lo que la proyección de casos a la semana 20 supera los 100,000 casos!!!

3⃣Según el Ministerio de Comercio Exterior y Turismo, esta semana santa se movilizarán 1,4M de peruanos durante la semana santa, lo cual, en la práctica, más de 1M de susceptibles se desplazarán a zonas calientes de dengue sirviendo como gatillo para la epidemia 2024, sin que el MINSA haya hecho una campaña efectiva para mitigar esto.

En conclusión, se alerta de que durante esta semana santa se observará un fenómeno de super contagio de dengue en las 20 regiones que presenten una transmisión activa de dengue con el consiguiente incremento acelerado de casos y fallecidos en las próximas semanas.

Saludos cordiales,

Antonio

14/11/2020

“Black Lives Matter Protests, Social Distancing, and COVID-19”

Sparked by the killing of George Floyd in police custody, the 2020 Black Lives Matter protests have brought a new wave of attention to the issue of inequality within criminal justice. However, many public health officials have warned that mass protests could lead to a reduction in social distancing behavior, spurring a resurgence of COVID-19. This study uses newly collected data on protests in 315 of the largest U.S. cities to estimate the impacts of mass protests on social distancing, COVID-19 case growth, and COVID-19-related deaths. Event-study analyses provide strong evidence that net stay-at-home behavior increased following protest onset, consistent with the hypothesis that non-protesters’ behavior was substantially affected by urban protests. This effect was not fully explained by the imposition of city curfews. Estimated effects were generally larger for persistent protests and those accompanied by media reports of violence. Furthermore, we find no evidence that urban protests reignited COVID-19 case or death growth after more than five weeks following the onset of protests. We conclude that predictions of population-level spikes in COVID-19 cases from Black Lives Matter protests were too narrowly conceived because of failure to account for non-participants’ behavioral responses to large gatherings.

Link: https://www.nber.org/papers/w27408

09/11/2020

"Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19"

Importance:
Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed.

Objective:
To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19.

Design, Setting, and Participants:
This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients.

Interventions:
Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237).

Main Outcomes and Measures:
The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality.

Results:
Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, −0.2% [95% CI, −5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09]).

Conclusions and Relevance:
Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults.

Trial Registration ClinicalTrials.gov: NCT04332991

Link: https://jamanetwork.com/journals/jama/fullarticle/2772922

07/11/2020

"Changes in Health Services Use Among Commercially Insured US Populations During the COVID-19 Pandemic"

Importance:
The coronavirus disease 2019 (COVID-19) pandemic has placed unprecedented strain on patients and health care professionals and institutions, but the association of the pandemic with use of preventive, elective, and nonelective care, as well as potential disparities in use of health care, remain unknown.

Objective:
To examine changes in health care use during the first 2 months of the COVID-19 pandemic in March and April of 2020 relative to March and April of 2019 and 2018, and to examine whether changes in use differ by patient’s zip code–level race/ethnicity or income.

Design, Setting, and Participants:
This cross-sectional study analyzed health insurance claims for patients from all 50 US states who receive health insurance through their employers. Changes in use of preventive services, nonelective care, elective procedures, prescription drugs, in-person office visits, and telemedicine visits were examined during the first 2 months of the COVID-19 pandemic in 2020 relative to existing trends in 2019 and 2018. Disparities in the association of the pandemic with health care use based on patient’s zip code–level race and income were also examined.

Results:
Data from 5.6, 6.4, and 6.8 million US individuals with employer-sponsored insurance in 2018, 2019, and 2020, respectively, were analyzed. Patient demographics were similar in all 3 years (mean [SD] age, 34.3 [18.6] years in 2018, 34.3 [18.5] years in 2019, and 34.5 [18.5] years in 2020); 50.0% women in 2018, 49.5% women in 2019, and 49.5% women in 2020). In March and April 2020, regression-adjusted use rate per 10 000 persons changed by −28.2 (95% CI, −30.5 to −25.9) and −64.5 (95% CI, −66.8 to −62.2) for colonoscopies; −149.1 (95% CI, −162.0 to −16.2) and −342.1 (95% CI, −355.0 to −329.2) for mammograms; −60.0 (95% CI, −63.3 to −54.7) and −118.1 (95% CI, −112.4 to −113.9) for hemoglobin A1c tests; −300.5 (95% CI, −346.5 to −254.5) and −369.0 (95% CI, −414.7 to −323.4) for child vaccines; −4.6 (95% CI, −5.3 to −3.9) and −10.9 (95% CI, −11.6 to −10.2) for musculoskeletal surgery; −1.1 (95% CI, −1.4 to −0.7) and −3.4 (95% CI, −3.8 to −3.0) for cataract surgery; −13.4 (95% CI, −14.6 to −12.2) and −31.4 (95% CI, −32.6 to −30.2) for magnetic resonance imaging; and −581.1 (95% CI, −612.9 to −549.3) and −1465 (95% CI, −1496 to −1433) for in-person office visits. Use of telemedicine services increased by 227.9 (95% CI, 221.7 to 234.1) per 10 000 persons and 641.6 (95% CI, 635.5 to 647.8) per 10 000 persons. Patients living in zip codes with lower-income or majority racial/ethnic minority populations experienced smaller reductions in in-person visits (≥80% racial/ethnic minority zip code: 200.0 per 10 000 [95% CI, 128.9-270.1]; 79%-21% racial/ethnic minority zip code: 54.2 per 10 000 [95% CI, 33.6-74.9]) but also had lower rates of adoption of telemedicine (≥80% racial/ethnic minority zip code: −71.6 per 10 000 [95% CI, −87.6 to −55.5]; 79%-21% racial/ethnic minority zip code: −15.1 per 10 000 [95% CI, −19.8 to −10.4]).

Conclusions and Relevance:
In this cross-sectional study of a large US population with employer-sponsored insurance, the first 2 months of the COVID-19 pandemic were associated with dramatic reductions in the use of preventive and elective care. Use of telemedicine increased rapidly but not enough to account for reductions in in-person primary care visits. Race and income disparities at the zip code level exist in use of telemedicine.

Link: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2772537

03/11/2020

“Dispersion of evaporating cough droplets in tropical outdoor environment”

The ongoing Covid-19 pandemic has focused our attention on airborne droplet transmission. In this study, we simulate the dispersion of cough droplets in a tropical outdoor environment, accounting for the effects of non-volatile components on droplet evaporation. The effects of relative humidity, wind speed, and social distancing on evaporative droplet transport are investigated. Transmission risks are evaluated based on SARS-CoV-2 viral deposition on a person standing 1 m or 2 m away from the cougher. Our results show that the travel distance for a 100 µm droplet can be up to 6.6 m under a wind speed of 2 m/s. This can be further increased under dry conditions. We found that the travel distance of a small droplet is relatively insensitive to relative humidity. For a millimetric droplet, the projected distance can be more than 1 m, even in still air. Significantly greater droplets and viral deposition are found on a body 1 m away from a cougher, compared to 2 m. Despite low inhalation exposure based on a single cough, infection risks may still manifest through successive coughs or higher viral loadings.

Link: https://aip.scitation.org/doi/10.1063/5.0026360

02/11/2020

“Age-specific mortality and immunity patterns of SARS-CoV-2”

Estimating the size and infection severity of the SARS-CoV-2 epidemic is made challenging by inconsistencies in available data. The number of COVID-19 deaths is often used as a key indicator for the epidemic size, but observed deaths represent only a minority of all infections1,2. Additionally, the heterogeneous burden in nursing homes and variable reporting of deaths in elderly individuals can hamper direct comparisons across countries of the underlying level of transmission and mortality rates3. Here we use age-specific COVID-19 death data from 45 countries and the results of 22 seroprevalence studies to investigate the consistency of infection and fatality patterns across multiple countries. We find that the age distribution of deaths in younger age groups (

02/11/2020

“Transmission of SARS-COV-2 Infections in Households — Tennessee and Wisconsin, April–September 2020”

What is already known about this topic?
Transmission of SARS-CoV-2 occurs within households; however, transmission estimates vary widely and the data on transmission from children are limited.

What is added by this report?
Findings from a prospective household study with intensive daily observation for ≥7 consecutive days indicate that transmission of SARS-CoV-2 among household members was frequent from either children or adults.

What are the implications for public health practice?
Household transmission of SARS-CoV-2 is common and occurs early after illness onset. Persons should self-isolate immediately at the onset of COVID-like symptoms, at the time of testing as a result of a high risk exposure, or at time of a positive test result, whichever comes first. All household members, including the index case, should wear masks within shared spaces in the household.

Link: https://www.cdc.gov/mmwr/volumes/69/wr/mm6944e1.htm?s_cid=mm6944e1_x

31/10/2020

"Remdesivir for the Treatment of Covid-19 — Final Report"

BACKGROUND
Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious.

METHODS
We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only.

RESULTS
A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P

30/10/2020

“Robust neutralizing antibodies to SARS-CoV-2 infection persist for months”

SARS-CoV-2 has caused a global pandemic with millions infected and numerous fatalities. Questions regarding the robustness, functionality, and longevity of the antibody response to the virus remain unanswered. Here we report that the vast majority of infected individuals with mild-to-moderate COVID-19 experience robust IgG antibody responses against the viral spike protein, based on a dataset of 30,082 individuals screened at Mount Sinai Health System in New York City. We also show that titers are relatively stable for at least a period approximating 5 months and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2. Our data suggests that more than 90% of seroconverters make detectible neutralizing antibody responses. These titers remain relatively stable for several months after infection.

Link: https://science.sciencemag.org/content/early/2020/10/27/science.abd7728

27/10/2020

“Declining prevalence of antibody positivity to SARS-CoV-2: a community study of 365,000 adults”

Background
The prevalence and persistence of antibodies following a peak SARS-CoV-2 infection provides insights into its spread in the community, the likelihood of reinfection and potential for some level of population immunity.

Methods
Prevalence of antibody positivity in England, UK (REACT2) with three cross-sectional surveys between late June and September 2020. 365104 adults used a self-administered lateral flow immunoassay (LFIA) test for IgG. A laboratory comparison of LFIA results to neutralization activity in panel of sera was performed.

Results
There were 17,576 positive tests over the three rounds. Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% [5.8, 6.1], to 4.8% [4.7, 5.0] and 4.4% [4.3, 4.5], a fall of 26.5% [-29.0, -23.8] over the three months of the study. There was a decline between rounds 1 and 3 in all age groups, with the highest prevalence of a positive result and smallest overall decline in positivity in the youngest age group (18-24 years: -14.9% [-21.6, -8.1]), and lowest prevalence and largest decline in the oldest group (75+ years: -39.0% [-50.8, -27.2]); there was no change in antibody positivity between rounds 1 and 3 in healthcare workers (+3.45% [-5.7, +12.7]). The decline from rounds 1 to 3 was largest in those who did not report a history of COVID- 19, (-64.0% [-75.6, -52.3]), compared to -22.3% ([-27.0, -17.7]) in those with SARS-CoV-2 infection confirmed on PCR.

Discussion
These findings provide evidence of variable waning in antibody positivity over time such that, at the start of the second wave of infection in England, only 4.4% of adults had detectable IgG antibodies using an LFIA. Antibody positivity was greater in those who reported a positive PCR and lower in older people and those with asymptomatic infection. These data suggest the possibility of decreasing population immunity and increasing risk of reinfection as detectable antibodies decline in the population.

Link:https://www.imperial.ac.uk/media/imperial-college/institute-of-global-health-innovation/MEDRXIV-2020-219725v1-Elliott.pdf

27/10/2020

“Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans”

Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10–15 d after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protection from reinfection.

Using sequential serum samples collected up to 94 d post onset of symptoms (POS) from 65 individuals with real-time quantitative PCR-confirmed SARS-CoV-2 infection, we show seroconversion (immunoglobulin (Ig)M, IgA, IgG) in >95% of cases and neutralizing antibody responses when sampled beyond 8 d POS. We show that the kinetics of the neutralizing antibody response is typical of an acute viral infection, with declining neutralizing antibody titres observed after an initial peak, and that the magnitude of this peak is dependent on disease severity.

Although some individuals with high peak infective dose (ID50 > 10,000) maintained neutralizing antibody titres >1,000 at >60 d POS, some with lower peak ID50 had neutralizing antibody titres approaching baseline within the follow-up period. A similar decline in neutralizing antibody titres was observed in a cohort of 31 seropositive healthcare workers.

The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection.

Link: https://www.nature.com/articles/s41564-020-00813-8

25/10/2020

“What you need to know about: Virology, transmission, and pathogenesis of SARS-CoV-2?”

1. SARS-CoV-2 is genetically similar to SARS-CoV-1, but characteristics of SARS-CoV-2—eg, structural differences in its surface proteins and viral load kinetics—may help explain its enhanced rate of transmission

2. In the respiratory tract, peak SARS-CoV-2 load is observed at the time of symptom onset or in the first week of illness, with subsequent decline thereafter indicating the highest infectiousness potential just before or within the first five days of symptom onset

3. Reverse transcription polymerase chain reaction (RT-PCR) tests can detect viral SARS-CoV-2 RNA in the upper respiratory tract for a mean of 17 days; however, detection of viral RNA does not necessarily equate to infectiousness, and viral culture from PCR positive upper respiratory tract samples has been rarely positive beyond nine days of illness

4. Symptomatic and pre-symptomatic transmission (1-2 days before symptom onset), is likely to play a greater role in the spread of SARS-CoV-2 than asymptomatic transmission

5. A wide range of virus-neutralising antibodies have been reported, and emerging evidence suggests that these may correlate with severity of illness but wane over time

Link: https://www.bmj.com/content/371/bmj.m3862

25/10/2020

“Increases in Loneliness Among Young Adults During the COVID-19 Pandemic and Association With Increases in Mental Health Problems”

Purpose:
Young adults are at high risk for increases in loneliness and mental health problems during the COVID-19 pandemic. The present study examined increases in loneliness in a young adult sample, for whom increases were greater, and association with increases in depression and anxiety.

Method:
Data from 564 young adults (ages 22–29, 60.7% women) were collected in January 2020 (pre-pandemic) and April/May 2020 (during pandemic).

Results:
Loneliness increased from January to April/May and changes in loneliness were greater for females, those with higher perceived social support in January, and those with greater concerns about the pandemic's social impacts. Depression (but not anxiety) increased during this time with changes in loneliness accounting for much of the increase in depression.

Conclusions:
Intervention strategies with young adults need to address loneliness and feelings of reduced social support during this time, especially for those who may have had greater disruption in their social lives.

Link: https://www.sciencedirect.com/science/article/pii/S1054139X20304924

24/10/2020

"Asymptomatic and Presymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infection Rates in a Multistate Sample of Skilled Nursing Facilities"

Asymptomatic transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be a major contributing factor in skilled nursing facility (SNF) outbreaks. However, limited knowledge exists regarding the prevalence of asymptomatic and presymptomatic infection in this setting. Although an estimated 40% to 45% of SARS-CoV-2 infections in the general population are asymptomatic at time of testing,1 a small number of US and international reports have documented higher asymptomatic rates in SNFs.2-5 We examined asymptomatic and presymptomatic infection rates in a large multistate sample of US SNFs, and examined variation in case counts by SARS-CoV-2 prevalence in the counties where SNFs are located.

Methods
We used data from Genesis HealthCare, a multistate long-term care provider with roughly 350 SNFs. By combining electronic medical record data with daily infection logs that recorded testing dates and results, we identified all unique resident cases of SARS-CoV-2 confirmed by polymerase chain reaction testing between March 16, 2020, and July 15, 2020. This study was approved by the Brown University institutional review board, which waived the requirement for participant informed consent because all data were deidentified.

All residents underwent nursing assessments at least twice daily. We classified residents as having new SARS-CoV-2–related symptoms if nurses documented in a structured change in condition note any of the symptoms listed in the eMethods in the Supplement. Residents were classified as symptomatic at presentation if they had new symptoms within 5 days before their first positive test date, presymptomatic if they had no symptoms in the 5 days before testing but developed symptoms within 14 days thereafter, and asymptomatic if they had no symptoms from 5 days pretest to 14 days posttest.

Test availability varied regionally and temporally. We analyzed cumulative case counts for SNFs that underwent 1 or more point-prevalence surveys, either facility-wide (all residents tested) or unit-based (all residents on specific units tested without testing the whole house). The cumulative case count includes cases detected during surveys plus those detected during symptom- or exposure-driven testing at any time from March 16, 2020, to July 15, 2020. We report the percentage of cumulative cases who were asymptomatic, presymptomatic, and symptomatic at presentation.

In addition, we describe variation in counts of combined asymptomatic and presymptomatic cases at time of initial survey for SNFs that underwent facility-wide testing, across counties located in the top 5%, middle 20%, and bottom 75% of US counties for SARS-CoV-2 prevalence. County data were obtained from the Johns Hopkins University Coronavirus Resource Center (https://coronavirus.jhu.edu).

Results
As of July 15, 2020, 182 SNFs in 20 states had at least 1 SARS-CoV-2 case and underwent some form of a point prevalence survey, with a cumulative total of 5403 unique resident cases (Table). Overall, 2194 (40.6%) cases were asymptomatic, 1033 (19.1%) were presymptomatic, and 2176 (40.3%) were symptomatic at presentation. The SNFs that underwent at least 1 facility-wide survey (N = 173) identified slightly higher cumulative rates of asymptomatic and presymptomatic infection than SNFs limited to unit-based surveys (N = 9) (P = .02). Of the 5011 cases identified in SNFs with facility-wide testing, 2049 (40.9%) were asymptomatic, 969 (19.3%) were presymptomatic, and 1993 (39.8%) were symptomatic at presentation. Of the 392 cases identified in SNFs with unit-based testing 145 (37.0%) were asymptomatic, 64 (16.3%) were presymptomatic, and 183 (46.7%) were symptomatic at presentation.

Among the 173 SNFs that underwent facility-wide surveys, those in counties with higher SARS-CoV-2 prevalence generally had higher combined counts of asymptomatic and presymptomatic cases at their initial survey than SNFs in counties with lower prevalence (Figure).

Discussion
We observed high asymptomatic and presymptomatic SARS-CoV-2 infection rates in a large multistate sample of SNFs, demonstrating the importance of universal testing for identifying and isolating cases. The SNFs located in areas with high SARS-CoV-2 prevalence detected higher numbers of asymptomatic and presymptomatic cases during initial point prevalence surveys, building on emerging evidence that SNF location is an important predictor of outbreaks.

Link: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2771816

This cross-sectional study examines the prevalence of asymptomatic and presymptomatic severe acute respiratory syndrome coronavirus 2 infection in skilled nursing facilities.

22/10/2020

"Face masks to prevent transmission of COVID-19: a systematic review and meta-analysis"

Background:
Based on the current status of the COVID-19 global pandemic, there is an urgent need to systematically evaluate the effectiveness of wearing masks to protect public health from COVID-19 infection.

Methods:
We conducted a systematic review and meta-analysis to evaluate the effectiveness of using face masks to prevent the spread of SARS-CoV-2. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI), VIP (Chinese) database. There were no language restrictions. This study was registered with PROSPERO under the number CRD42020211862.

Results:
A total of 6 case-control studies were included. In general, wearing a mask was associated with a significantly reduced risk of COVID-19 infection (OR = 0.38, 95% CI = 0.21-0.69, I2 = 54.1%). Heterogeneity modifiers were investigated by subgroup analysis. For healthcare workers group, masks were shown to have a reduce risk of infection by nearly 70%. Studies in China showed a higher protective effect than other countries. Adjusted estimates and subgroup analyses showed similar findings.

Conclusions:
The results of this systematic review and meta-analysis support the conclusion that wearing a mask could reduce the risk of COVID-19 infection.

Link: https://www.medrxiv.org/content/10.1101/2020.10.16.20214171v1

20/10/2020

"Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia - A Randomized Clinical Trial"

Importance:
Severe pneumonia with hyperinflammation and elevated interleukin-6 is a common presentation of coronavirus disease 2019 (COVID-19).

Objective:
To determine whether tocilizumab (TCZ) improves outcomes of patients hospitalized with moderate-to-severe COVID-19 pneumonia.

Design, Setting, and Particpants:
This cohort-embedded, investigator-initiated, multicenter, open-label, bayesian randomized clinical trial investigating patients with COVID-19 and moderate or severe pneumonia requiring at least 3 L/min of oxygen but without ventilation or admission to the intensive care unit was conducted between March 31, 2020, to April 18, 2020, with follow-up through 28 days. Patients were recruited from 9 university hospitals in France. Analyses were performed on an intention-to-treat basis with no correction for multiplicity for secondary outcomes.

Interventions:
Patients were randomly assigned to receive TCZ, 8 mg/kg, intravenously plus usual care on day 1 and on day 3 if clinically indicated (TCZ group) or to receive usual care alone (UC group). Usual care included antibiotic agents, antiviral agents, corticosteroids, vasopressor support, and anticoagulants.

Main Outcomes and Measures:
Primary outcomes were scores higher than 5 on the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) on day 4 and survival without need of ventilation (including noninvasive ventilation) at day 14. Secondary outcomes were clinical status assessed with the WHO-CPS scores at day 7 and day 14, overall survival, time to discharge, time to oxygen supply independency, biological factors such as C-reactive protein level, and adverse events.

Results:
Of 131 patients, 64 patients were randomly assigned to the TCZ group and 67 to UC group; 1 patient in the TCZ group withdrew consent and was not included in the analysis. Of the 130 patients, 42 were women (32%), and median (interquartile range) age was 64 (57.1-74.3) years. In the TCZ group, 12 patients had a WHO-CPS score greater than 5 at day 4 vs 19 in the UC group (median posterior absolute risk difference [ARD] −9.0%; 90% credible interval [CrI], −21.0 to 3.1), with a posterior probability of negative ARD of 89.0% not achieving the 95% predefined efficacy threshold. At day 14, 12% (95% CI −28% to 4%) fewer patients needed noninvasive ventilation (NIV) or mechanical ventilation (MV) or died in the TCZ group than in the UC group (24% vs 36%, median posterior hazard ratio [HR] 0.58; 90% CrI, 0.33-1.00), with a posterior probability of HR less than 1 of 95.0%, achieving the predefined efficacy threshold. The HR for MV or death was 0.58 (90% CrI, 0.30 to 1.09). At day 28, 7 patients had died in the TCZ group and 8 in the UC group (adjusted HR, 0.92; 95% CI 0.33-2.53). Serious adverse events occurred in 20 (32%) patients in the TCZ group and 29 (43%) in the UC group (P = .21).

Conclusions and Relevance:
In this randomized clinical trial of patients with COVID-19 and pneumonia requiring oxygen support but not admitted to the intensive care unit, TCZ did not reduce WHO-CPS scores lower than 5 at day 4 but might have reduced the risk of NIV, MV, or death by day 14. No difference on day 28 mortality was found. Further studies are necessary for confirming these preliminary results.

Trial Registration:
ClinicalTrials.gov Identifier: NCT04331808

Link: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2772187