Background Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19). Methods We conducted a randomized, open-label, phase 3 trial involving hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation of 94% or less while they were breathing ambient air, and radiologic evidence of pneumonia. Patients were randomly assigned in a 1:1 ratio to receive intravenous remdesivir for either 5 days or 10 days. All patients received 200 mg of remdesivir on day 1 and 100 mg once daily on subsequent days. The primary end point was clinical status on day 14, assessed on a 7-point ordinal scale. Results In total, 397 patients underwent randomization and began treatment (200 patients for 5 days and 197 for 10 days). The median duration of treatment was 5 days (interquartile range, 5 to 5) in the 5-day group and 9 days (interquartile range, 5 to 10) in the 10-day group. At baseline, patients randomly assigned to the 10-day group had significantly worse clinical status than those assigned to the 5-day group (P=0.02). By day 14, a clinical improvement of 2 points or more on the ordinal scale occurred in 64% of patients in the 5-day group and in 54% in the 10-day group. After adjustment for baseline clinical status, patients in the 10-day group had a distribution in clinical status at day 14 that was similar to that among patients in the 5-day group (P=0.14). The most common adverse events were nausea (9% of patients), worsening respiratory failure (8%), elevated alanine aminotransferase level (7%), and constipation (7%). Conclusions In patients with severe Covid-19 not requiring mechanical ventilation, our trial did not show a significant difference between a 5-day course and a 10-day course of remdesivir. With no placebo control, however, the magnitude of benefit cannot be determined. (Funded by Gilead Sciences; GS-US-540-5773 ClinicalTrials.gov number, NCT04292899 .)

IMPORTANCE Remdesivir demonstrated clinical benefit in a placebo-controlled trial in patients with severe coronavirus disease 2019 (COVID-19), but its effect in patients with moderate disease is unknown. OBJECTIVE To determine the efficacy of 5 or 10 days of remdesivir treatment compared with standard care on clinical status on day 11 after initiation of treatment. DESIGN, SETTING, AND PARTICIPANTS Randomized, open-label trial of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (pulmonary infiltrates and room-air oxygen saturation >94%) enrolled from March 15 through April 18, 2020, at 105 hospitals in the United States, Europe, and Asia. The date of final follow-up was May 20, 2020. INTERVENTIONS Patients were randomized in a 1:1:1 ratio to receive a 10-day course of remdesivir (n = 197), a 5-day course of remdesivir (n = 199), or standard care (n = 200). Remdesivir was dosed intravenously at 200 mg on day 1 followed by 100 mg/d. MAIN OUTCOMES AND MEASURES The primary end point was clinical status on day 11 on a 7-point ordinal scale ranging from death (category 1) to discharged (category 7). Differences between remdesivir treatment groups and standard care were calculated using proportional odds models and expressed as odds ratios. An odds ratio greater than 1 indicates difference in clinical status distribution toward category 7 for the remdesivir group vs the standard care group. RESULTS Among 596 patients who were randomized, 584 began the study and received remdesivir or continued standard care (median age, 57 [interquartile range, 46-66] years; 227 [39%] women; 56% had cardiovascular disease, 42% hypertension, and 40% diabetes), and 533 (91%) completed the trial. Median length of treatment was 5 days for patients in the 5-day remdesivir group and 6 days for patients in the 10-day remdesivir group. On day 11, patients in the 5-day remdesivir group had statistically significantly higher odds of a better clinical status distribution than those receiving standard care (odds ratio, 1.65; 95% CI, 1.09-2.48; P = .02). The clinical status distribution on day 11 between the 10-day remdesivir and standard care groups was not significantly different (P = .18 by Wilcoxon rank sum test). By day 28, 9 patients had died: 2 (1%) in the 5-day remdesivir group, 3 (2%) in the 10-day remdesivir group, and 4 (2%) in the standard care group. Nausea (10% vs 3%), hypokalemia (6% vs 2%), and headache (5% vs 3%) were more frequent among remdesivir-treated patients compared with standard care. CONCLUSIONS AND RELEVANCE Among patients with moderate COVID-19, those randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with standard care at 11 days after initiation of treatment. Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance.

Introduction Data on people living with human immunodeficiency virus (PLWH) in the current SARS-CoV-2 pandemic are still scarce. This case series of 33 PLWH patients with COVID-19 reveals symptoms and outcome in this special population. Methods Retrospective analysis of anonymized data including age, gender, HIV-associated parameters, symptoms, and outcome. Results Three out of 32 patients with documented outcomes died (9%). 91% of the patients recovered and 76% have been classified as mild cases. All patients were on antiretroviral treatment, of them 22 on tenofovir-containing regimen and 4 on the protease inhibitor darunavir. Conclusions This preliminary case series does not support excess morbidity and mortality among symptomatic COVID-19 PLWH and with viral suppression on ART. SARS-CoV-2 infections may occur during boosted darunavir-based and/or on tenofovir-containing ART.

Background Monkeypox is a zoonotic orthopoxvirus infection endemic in central and western Africa. In May 2022, human monkeypox infections including human-to-human transmission were reported in a multi-country outbreak in Europe and North America. Case presentations Here we present the first two cases of monkeypox infection in humans diagnosed in Germany. We present clinical and virological findings, including the detection of monkeypox virus DNA in blood and semen. The clinical presentation and medical history of our patients suggest close physical contact during sexual interactions as the route of infection. Conclusion Monkeypox requires rapid diagnosis and prompt public health response. The disease should be considered in the current situation especially the differential diagnosis of vesicular or pustular rash, particularly in patients with frequent sexual contacts. Most importantly, it is essential to raise awareness among all health professionals for the rapid and correct recognition and diagnosis of this disease, which is probably still underreported in Europe (Adler et al. in Lancet Infect Dis https://doi.org/10.1016/s1473-3099(22)00228-6, 2022).

Continuous and intermittent PrEP demonstrated high efficacy in preventing HIV seroconversion, notably among MSM. PrEP was well tolerated. Adherence was critical for high efficacy in all studies. Further studies to evaluate implementation strategies and cost-effectiveness in different risk populations are needed as well as drug approval in Europe.

Objectives A prior T cell depletion induced by HIV infection may carry deleterious consequences in the current COVID‐19 pandemic. Clinical data on patients co‐infected with HIV and SARS‐CoV‐2 are still scarce. Methods This multicentre cohort study evaluated risk factors for morbidity and mortality of COVID‐19 in people living with HIV (PLWH), infected with SARS‐CoV‐2 in three countries in different clinical settings. COVID‐19 was clinically classified as to be mild‐to‐moderate or severe. Results Of 175 patients, 49 (28%) had severe COVID‐19 and 7 (4%) patients died. Almost all patients were on antiretroviral therapy (ART) and in 94%, HIV RNA was below 50 copies/mL prior to COVID‐19 diagnosis. In the univariate analysis, an age 50 years or older, a CD4+ T cell nadir of < 200/µl, current CD4+ T cells < 350/µl and the presence of at least one comorbidity were significantly associated with severity of COVID‐19. No significant association was found for gender, ethnicity, obesity, a detectable HIV RNA, a prior AIDS‐defining illness, or tenofovir (which was mainly given as alafenamide) or protease inhibitor use in the current ART. In a multivariate analysis, the only factor associated with risk for severe COVID‐19 was a current CD4+ T cell count of < 350/µl (adjusted odds ratio 2.85, 95% confidence interval 1.26‐6.44, p=0.01). The only factor associated with mortality was a low CD4 T cell nadir. Conclusions In PLWH, immune deficiency is a possible risk factor for severe COVID‐19, even in the setting of virological suppression. There is no evidence for a protective effect of PIs or tenofovir alafenamide.

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Bacterial co-infections are associated with unfavourable outcomes in respiratory viral infections; however, microbiological and antibiotic data related to COVID-19 are sparse. Adequate use of antibiotics in line with antibiotic stewardship (ABS) principles is warranted during the pandemic. We performed a retrospective study of clinical and microbiological characteristics of 140 COVID-19 patients admitted between February and April 2020 to a German University hospital, with a focus on bacterial co-infections and antimicrobial therapy. The final date of follow-up was 6 May 2020. Clinical data of 140 COVID-19 patients were recorded: The median age was 63.5 (range 17–99) years; 64% were males. According to the implemented local ABS guidelines, the most commonly used antibiotic regimen was ampicillin/sulbactam (41.5%) with a median duration of 6 (range 1–13) days. Urinary antigen tests for Legionella pneumophila and Streptococcus peumoniae were negative in all cases. In critically ill patients admitted to intensive care units (n = 50), co-infections with Enterobacterales (34.0%) and Aspergillus fumigatus (18.0%) were detected. Blood cultures collected at admission showed a diagnostic yield of 4.2%. Bacterial and fungal co-infections are rare in COVID-19 patients and are mainly prevalent in critically ill patients. Further studies are needed to assess the impact of antimicrobial therapy on therapeutic outcome in COVID-19 patients to prevent antimicrobial overuse. ABS guidelines could help in optimising the management of COVID-19. Investigation of microbial patterns of infectious complications in critically ill COVID-19 patients is also required.

ZusammenfassungSeit Dezember 2019 verbreitet sich das neuartige Coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome – Corona Virus-2) rasch im Sinne einer weltweiten Pandemie. Dies stellt Kliniker und Krankenhäuser vor große Herausforderungen und belastet die Gesundheitssysteme vieler Länder in einem nie dagewesenen Ausmaß. Die Mehrheit der Patienten mit Coronavirus Disease 2019 (COVID-19) zeigt lediglich milde Symptome wie Husten und Fieber. Allerdings benötigen etwa 8 % eine stationäre Behandlung. Der frühzeitigen Klärung, ob eine stationäre und ggfs. intensivmedizinische Behandlung medizinisch sinnvoll und vom Patienten gewollt ist, kommt in der Pandemie eine besondere Bedeutung zu. Die akute hypoxämische respiratorische Insuffizienz mit Dyspnoe und hoher Atemfrequenz (> 30/min) führt i. d. R. zur Aufnahme auf die Intensivstation. Oft finden sich dann bereits bilaterale pulmonale Infiltrate/Konsolidierungen oder auch Lungenembolien in der Bildgebung. Im weiteren Verlauf entwickeln einige dieser Patienten ein akutes Lungenversagen (Acute Respiratory Distress Syndrome; ARDS). Eine Sterblichkeitsreduktion einer verfügbaren medikamentösen Therapie bei schwerer COVID-19-Erkrankung ist bisher lediglich für Dexamethason in randomisiert, kontrollierten Studien nachgewiesen. Das Hauptziel der supportiven Therapie besteht in der Sicherstellung einer ausreichenden Oxygenierung. Die invasive Beatmung und wiederholte Bauchlagerung sind dabei wichtige Elemente in der Behandlung von schwer hypoxämischen COVID-19-Patienten. Die strikte Einhaltung der Basishygiene, einschließlich der Händehygiene, sowie das korrekte Tragen von adäquater persönlicher Schutzausrüstung sind im Umgang mit den Patienten unabdingbar. Medizinisch notwendige Handlungen am Patienten, die zur Aerosolbildung führen könnten, sollten mit äußerster Sorgfalt und Vorbereitung durchgeführt werden.