Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients

Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when = 50 years and symptomatic for <= 7days were included. The intervention consisted of 200-300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311); OR for hospitalization or death was 0.919 (CI 0.592-1.416). CP effect on hospital admission or death was largest in patients with <= 5 days of symptoms (OR 0.658, 95%CI 0.394-1.085). CP did not decrease the time to full symptom resolution

Calidad de vida de las mujeres de edad avanzada en México

A partir de los resultados del XII Censo en el año 2000, se confirmó un cambio en la estructura poblacional, esto debido a la disminución de las tasas de mortalidad y de un aumento considerable de la esperanza de vida en los últimos años. De este modo se observó que la esperanza de vida se ha duplicado desde principios del siglo pasado. El aumento de la esperanza de vida junto con otros cambios importantes tales como la disminución de la tasa de fecundidad y de una menor mortalidad tuvieron por consecuencia que una población llegue a la etapa final de la transición demográfica. De este modo se discutirán algunos factores que en México propiciaron estos cambios. A partir de estos antecedentes, se planteó la siguiente hipótesis. En el presente trabajo se trató de comprobar que aunque la mujer espera vivir más tiempo que el hombre, es ella quién vive más tiempo con enfermedades y dependiente de otras personas. Es decir, la calidad de vida femenina, hablando en términos estrictamente saludables, sobre todo en edades avanzadas, es más deficiente que la del sexo opuesto. Debido a la hipótesis mencionada anteriormente, se definió que la población objetivo de estudio es la mujer mayor de 65 años en México. Sin embargo, y para fines de comparación entre la población femenina y masculina, se realizaron los mismos cálculos para ambos sexos. A partir de estos antecedentes y de este planteamiento del problema a estudiar, se discutirán algunos puntos acerca de la vejez, desde el punto de vista de la salud. Además se mencionarán algunos esfuerzos a nivel mundial por mejorar la situación de la mujer. A continuación se presenta la situación demográfica de México a partir de la pirámide poblacional correspondiente a 1970 y el año 2000 en la cual se mostrará el gran cambio ocurrido en términos demográficos. Finalmente, y con el objetivo de comprobar la hipótesis planteada anteriormente, se realizó una tabla de mortalidad tanto femenina como masculina, para que a partir de ella, se realizaran los cálculos correspondientes de la esperanza de vida saludable y la esperanza de vida activa para ambos sexos, previa definición de estas esperanzas y explicación del método Sullivan el cual fue utilizado para realizar los cálculos correspondientes. Es importante señalar que las principales bases de datos que se usaron fueron una encuesta llamada "Mexican Health and Aging Study, MHAS" por sus siglas en inglés, así como las estadísticas vitalicias correspondientes a los años 2000 y 2001, en especial los nacimientos y defunciones. Estas estadísticas corresponden al total de la población en México, ya que dichos datos provienen del registro civil, y por lo tanto no excluyen a ningún sector de la población. Es importante señalar aquí que los resultados obtenidos en esta investigación corresponden al año 2001 debido a que la encuesta MHAS fue realizada a mediados del mismo año. Entonces, a través de este método, fue posible encontrar la esperanza de vida saludable y la esperanza de vida activa tanto para mujeres como para hombres por grupos quinquenales, y como se sabe que en la vida real las personas no viven por ejemplo, exactamente los x años estimados, fue necesario calcular intervalos de confianza de las esperanzas estimadas de modo que una persona tuviera un 95% de probabilidad de vivir los años indicados en el intervalo en estado saludable o activo. Finalmente, puesto que se quiere demostrar que la calidad de vida de la mujer es más deficiente que la del hombre es necesario comprobar que efectivamente la esperanza de vida saludable y activa de la mujer es menor que la del hombre. Para este fin, se realizaron pruebas de hipótesis con un nivel de significacia de 0.05 donde la hipótesis nula era que la esperanza de vida saludable o activa femenina era igual que la masculina y la hipótesis alternativa era que la esperanza de vida saludable o activa femenina era menor que la correspondiente a la del sexo opuesto. Finalmente, algunas de las principales conclusiones a las que se llegaron a través de esta investigación fueron que en el año 2001, al nacer, la mujer esperaba vivir 5 años más que el hombre. Por otra parte, en edades no muy avanzadas la mujer esperaba vivir más años en estado activo que el hombre, sin embargo, es en la senectud cuando los hombres esperan vivir más años que las mujeres de manera independiente. Además, en materia de salud, es el hombre quien a lo largo de los distintos grupos quinquenales espera vivir más años con buena salud. Aunque en edades avanzadas estas diferencias sean poco significativas. Por último, se concluyó que la calidad de vida de las mujeres de edad avanzada es más deficiente porque los hombres tienen mayor esperanza de años saludables y porque a partir de los 65 años, son los hombres quienes esperan vivir más tiempo sin ningún tipo de discapacidad que le impida realizar sus actividades cotidianas

Evaluating the accuracy of self-collected swabs for the diagnosis of monkeypox.

We evaluated the accuracy of patient-collected skin lesions, oropharyngeal, and rectal swabs amongst 50 individuals enrolled in a study of monkeypox viral dynamics. We found that the performance of self-collected samples was similar to that of physician-collected samples, suggesting that self-sampling is a reliable strategy for diagnosing monkeypox

Clinical presentation and virological assessment of confirmed human monkeypox virus cases in Spain: a prospective observational cohort study.

BACKGROUND: In May, 2022, several European countries reported autochthonous cases of monkeypox, which rapidly spread globally. Early reports suggest atypical presentations. We aimed to investigate clinical and virological characteristics of cases of human monkeypox in Spain. METHODS: This multicentre, prospective, observational cohort study was done in three sexual health clinics in Madrid and Barcelona, Spain. We enrolled all consecutive patients with laboratory-confirmed monkeypox from May 11 to June 29, 2022. Participants were offered lesion, anal, and oropharynx swabs for PCR testing. Participant data were collected by means of interviews conducted by dermatologists or specialists in sexually transmitted infections and were recorded using a standard case report form. Outcomes assessed in all participants with a confirmed diagnosis were demographics, smallpox vaccination, HIV status, exposure to someone with monkeypox, travel, mass gathering attendance, risk factors for sexually transmitted infections, sexual behaviour, signs and symptoms on first presentation, virological results at multiple body sites, co-infection with other sexually transmitted pathogens, and clinical outcomes 14 days after the initial presentation. Clinical outcomes were followed up until July 13, 2022. FINDINGS: 181 patients had a confirmed monkeypox diagnosis and were enrolled in the study. 166 (92%) identified as gay men, bisexual men, or other men who have sex with men (MSM) and 15 (8%) identified as heterosexual men or heterosexual women. Median age was 37·0 years (IQR 31·0-42·0). 32 (18%) patients reported previous smallpox vaccination, 72 (40%) were HIV-positive, eight (11%) had a CD4 cell count less than 500 cells per μL, and 31 (17%) were diagnosed with a concurrent sexually transmitted infection. Median incubation was 7·0 days (IQR 5·0-10·0). All participants presented with skin lesions; 141 (78%) participants had lesions in the anogenital region, and 78 (43%) in the oral and perioral region. 70 (39%) participants had complications requiring treatment: 45 (25%) had a proctitis, 19 (10%) had tonsillitis, 15 (8%) had penile oedema, six (3%) an abscess, and eight (4%) had an exanthem. Three (2%) patients required hospital admission. 178 (99%) of 180 swabs from skin lesions collected tested positive, as did 82 (70%) of 117 throat swabs. Viral load was higher in lesion swabs than in pharyngeal specimens (mean cycle threshold value 23 [SD 4] vs 32 [6], absolute difference 9 [95% CI 8-10]; p<0·0001). 108 (65%) of 166 MSM reported anal-receptive sex. MSM who engaged in anal-receptive sex presented with proctitis (41 [38%] of 108 vs four [7%] of 58, absolute difference 31% [95% CI 19-44]; p<0·0001) and systemic symptoms before the rash (67 [62%] vs 16 [28%], absolute difference 34% [28-62]; p<0·0001) more frequently than MSM who did not engage in anal-receptive sex. 18 (95%) of 19 participants with tonsillitis reported practising oral-receptive sex. The median time from onset of lesions to formation of a dry crust was 10 days (IQR 7-13). INTERPRETATION: In our cohort, monkeypox caused genital, perianal, and oral lesions and complications including proctitis and tonsillitis. Because of the variability of presentations, clinicians should have a low threshold for suspicion of monkeypox. Lesion swabs showed the highest viral loads, which, combined with the history of sexual exposure and the distribution of lesions, suggests close contact is probably the dominant transmission route in the current outbreak. FUNDING: None

Viral dynamics in patients with monkeypox infection: a prospective cohort study in Spain.

BACKGROUND: Monkeypox DNA has been detected in skin lesions, saliva, oropharynx, urine, semen, and stool of patients infected during the 2022 clade IIb outbreak; however, the viral dynamics within these compartments remain unknown. We aimed to characterise the viral load kinetics over time in various parts of the body. METHODS: This was an observational, prospective, multicentre study of outpatients diagnosed with monkeypox in two hospitals and two sexual health clinics in Spain between June 28, 2022, and Sept 22, 2022. Men and women aged over 18 years were eligible if they reported having symptom onset within the previous 10 days of presentation, and were ineligible if disease was severe enough to be admitted to hospital. Samples were collected from five body locations (skin lesions, oropharynx, rectum, semen or vagina, and a dried blood spot) at six time points up to 57 days after the screening visit. Samples were analysed by quantitative PCR and a subset by cell culture. The primary endpoint was time from symptom onset to viral DNA clearance. FINDINGS: Overall, 1663 samples were collected from 77 study participants. 75 (97%) participants were men, the median age was 35·0 years (IQR 29·0-46·0), and 39 (51%) participants were living with HIV. The median time from symptom onset to viral clearance was 25 days (95% CI 23-28) in the skin lesions, 16 days (13-19) in the oropharynx, 16 days (13-23) in the rectum, 13 days in semen (9-18), and 1 day in blood (0-5). The time from symptom onset to viral clearance for 90% of cases was 41 days (95% CI 34-47) in skin lesions and 39 days (27-56) in semen. The median viral load in skin lesions was 7·3 log10 copies per mL (IQR 6·5-8·2) at baseline, compared with 4·6 log10 copies per mL (2·9-5·8) in oropharyngeal samples, 5·0 log10 copies per mL (2·9-7·5) in rectal samples, 3·5 log10 copies per mL (2·9-4·7) in semen samples, and 4·0 log10 copies per mL (4·0-4·0) in blood specimens. Replication-competent viruses were isolated in samples with high DNA levels (>6·5 log10 copies per mL). INTERPRETATION: In immunocompetent patients with mild monkeypox disease, PCR data alone would suggest a contact isolation period of 3 to 6 weeks but, based on detection of replication-competent virus, this time could be reduced. Based on findings from this cohort of patients, semen testing and prolonged use of condoms after recovery from monkeypox might not be necessary. FUNDING: University Hospital Germans Trias i Pujol and the YoMeCorono. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section

Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trialResearch in context

Summary: Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, −3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; −9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols