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Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity—but also aided in the control—of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6–8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples—in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19. Detailed virological analysis of nine cases of coronavirus disease 2019 (COVID-19) provides proof of active replication of the SARS-CoV-2 virus in tissues of the upper respiratory tract.

The severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) has emerged as the infectious agent causing the pandemic coronavirus disease 2019 (COVID-19) with dramatic consequences for global human health and economics. Previously, we reached clinical evaluation with our vector vaccine based on vaccinia virus MVA against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes an infection in humans similar to SARS and COVID-19. Here, we describe the construction and preclinical characterization of a recombinant MVA expressing full-length SARS-CoV-2 spike (S) protein (MVA-SARS-2-S). Genetic stability and growth characteristics of MVA-SARS-2-S, plus its robust synthesis of S antigen, make it a suitable candidate vaccine for industrial scale production. Vaccinated mice produced S antigen-specific CD8+ T cells and serum antibodies binding to S glycoprotein that neutralized SARS-CoV-2. Prime-boost vaccination with MVA-SARS-2-S protected mice sensitized with a human ACE2-expressing adenovirus from SARS-CoV-2 infection. MVA-SARS-2-S is currently being investigated in a phase I clinical trial as aspirant for developing a safe and efficacious vaccine against COVID-19.Significance StatementThe highly attenuated vaccinia virus MVA is licensed as smallpox vaccine, and as vector it is a component of the approved Adenovirus-MVA-based prime-boost vaccine against Ebola virus disease. Here we provide results from testing the COVID-19 candidate vaccine MVA-SARS-2-S, a poxvirus-based vector vaccine that proceeded to clinical evaluation. When administered by intramuscular inoculation, MVA-SARS-2-S expresses and safely delivers the full-length SARS-CoV-2 spike (S) protein, inducing balanced SARS-CoV-2-specific cellular and humoral immunity, and protective efficacy in vaccinated mice. Substantial clinical experience has already been gained with MVA vectors using homologous and heterologous prime-boost applications, including the immunization of children and immunocompromised individuals. Thus, MVA-SARS-2-S represents an important resource for developing further optimized COVID-19 vaccines.

Wir berichten uber das gehaufte Auftreten von Riechstorungen bei COVID-19-Patienten in der ersten Gruppe von COVID-19-Patienten in Deutschland (Webasto-Cluster). Uber den Verlust des Geruch- und/oder Geschmackssinns berichteten 26 von 63 COVID-19-Patienten (41 %), wobei nur bei 31 % der von Hyposmie Betroffenen gleichzeitig Symptome einer Rhinitis vorlagen. Bei 14 Patienten fuhrten wir einen Riechtest und bei 10 einen Schmecktest durch. Die Messungen fanden innerhalb der Krankenversorgung einer fruhen COVID-19-Kohorte statt. Bei 10/14 Patienten lag sowohl vor als auch nach Abschwellen der Nasenschleimhaute eine Riechstorung vor. Fur 2/14 Patienten war die Hyposmie das fuhrende oder sogar das einzige Symptom der SARS-CoV-2-Infektion. Alle Getesteten berichteten uber eine Besserung des Geruchs- und/oder Geschmackssinns innerhalb von 8–23 Tagen. Den vorliegenden Daten zufolge a) kann COVID-19 bei einer nennenswerten Anzahl Patienten zu Hyposmie fuhren, die Inzidenz betrug ca. 30 % in dieser Kohorte; b) war die Riechstorung uberwiegend nicht mit rhinitischen Symptomen assoziiert, was auf eine nichtrhinitische, z. B. neurogene Ursache hinweisen kann; und c) erholte das Riechvermogen sich weitgehend im Laufe von 1–3 Wochen nach Beginn der COVID-19-Symptome. Anhaltspunkte fur ein gehauftes Auftreten einer Schmeckstorung ergaben sich nicht. Diese fruhen Ergebnisse konnen sowohl bei der Interpretation der COVID-19-assoziierten Hyposmie als auch fur ein beruhigendes Patentengesprach angesichts der hier beobachteten temporaren Natur der Hyposmie hilfreich sein. Daruber hinaus kann nach derzeitiger Erfahrung eine plotzlich aufgetretene Hyposmie ohne Vorliegen einer neuen Nasenatmungsbehinderung (Rhinitis) das fuhrende oder sogar einzige Symptom einer SARS-CoV-2-Infektion sein.

Coronavirus disease 2019 (COVID-19) is an acute respiratory tract infection that emerged in late 20191,2. Initial outbreaks in China involved 13.8% cases with severe-, and 6.1% with critical courses3. This severe presentation corresponds to the usage of a virus receptor that is expressed predominantly in the lung2,4. By causing an early onset of severe symptoms, this same receptor tropism is thought to have determined pathogenicity but also aided the control of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of COVID-19 cases with mild upper respiratory tract symptoms, suggesting a potential for pre- or oligosymptomatic transmission6-8. There is an urgent need for information on body site - specific virus replication, immunity, and infectivity. Here we provide a detailed virological analysis of nine cases, providing proof of active virus replication in upper respiratory tract tissues. Pharyngeal virus shedding was very high during the first week of symptoms (peak at 7.11 × 108 RNA copies per throat swab, day 4). Infectious virus was readily isolated from throat- and lung-derived samples, but not from stool samples in spite of high virus RNA concentration. Blood and urine never yielded virus. Active replication in the throat was confirmed by viral replicative RNA intermediates in throat samples. Sequence-distinct virus populations were consistently detected in throat- and lung samples of one same patient. Shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 6-12 days, but was not followed by a rapid decline of viral loads. COVID-19 can present as a mild upper respiratory tract illness. Active virus replication in the upper respiratory tract puts prospects of COVID-19 containment in perspective.

2019-nCoV Transmission from Asymptomatic Patient In this report, investigators in Germany detected the spread of the novel coronavirus (2019-nCoV) from a person who had recently traveled from China...

Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 2019

Deutschland verzeichnete 2015 einen Zuwachs des Fluchtlingsstroms auf etwa 1 Mio. Menschen. Die medizinische Versorgung dieser Patientengruppe birgt einige Besonderheiten, die sich von der medizinischen Versorgung der einheimischen Bevolkerung grundlegend unterscheiden. Katastrophale hygienische Bedingungen wahrend der Flucht sowie Mangel- und Fehlernahrung fuhren zu einer erhohten Krankheitsmorbiditat, insbesondere hinsichtlich Infektionserkrankungen. Ziel dieser Ubersichtsarbeit ist es, anhand eigener Daten sowie der bisher verfugbaren Literatur (nach Pubmed-Recherche) diese Spezifika in der medizinischen Versorgung von Fluchtlingen herauszuarbeiten. Ergebnisse Die Fluchtlinge sind uberwiegend mannlich (65 %), der Altersmedian betragt

Background | Relapsing fever is divided into tick borne relapsing fever (TBRF) and louse borne relapsing fever (LBRF). This report describes 25 refugees from East Africa who were diagnosed to suffer from LBRF within a period of 6 month only at a single hospital in Munich / Germany. Material & Methods | The aim was to point out common clinical features as well as laboratory findings and clinical symptoms before and after initiation of treatment in 25 patients with louse borne relapsing fever (LBRF) who were diagnosed and treated at Klinikum Munchen Schwabing from August 2015 to January 2016. To the best of our knowledge this is the largest case series of LBRF in the western world for decades. Main focus of the investigation was put on clinical aspects. Results | All 25 patients suffered from acute onset of high fever with chills, headache and severe prostration. Laboratory analysis showed high CRP and a marked thrombocytopenia. A Giemsa blood stain was procured immediately in order to look for malaria. In the blood smear spirochetes with typical shape and aspect of borrelia species could be detected.The further PCR analysis confirmed infection with Borrelia recurrentis. Treatment with Doxycycline was started forthwith. The condition improved already on the second day after treatment was started and all were restored to health in less than a week. Apart from a mild to moderate Jarisch-Herxheimer-reaction we didn`t see any side effects of the therapy. Conclusion | LBRF has to be taken into account in feverish patients who come as refugees from East-Africa. It seems that our patients belong to a cluster which probably has its origin in Libya and more patients are to be expected in the near future. As LBRF might cause outbreaks in refugee camps it is pivotal to be aware of this emerging infectious disease in refugees from East-Africa.

Summary Background The Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging virus involved in cases and case clusters of severe acute respiratory infection in the Arabian Peninsula, Tunisia, Morocco, France, Italy, Germany, and the UK. We provide a full description of a fatal case of MERS-CoV infection and associated phylogenetic analyses. Methods We report data for a patient who was admitted to the Klinikum Schwabing (Munich, Germany) for severe acute respiratory infection. We did diagnostic RT-PCR and indirect immunofluorescence. From time of diagnosis, respiratory, faecal, and urine samples were obtained for virus quantification. We constructed a maximum likelihood tree of the five available complete MERS-CoV genomes. Findings A 73-year-old man from Abu Dhabi, United Arab Emirates, was transferred to Klinikum Schwabing on March 19, 2013, on day 11 of illness. He had been diagnosed with multiple myeloma in 2008, and had received several lines of treatment. The patient died on day 18, due to septic shock. MERS-CoV was detected in two samples of bronchoalveolar fluid. Viral loads were highest in samples from the lower respiratory tract (up to 1·2 × 106 copies per mL). Maximum virus concentration in urine samples was 2691 RNA copies per mL on day 13; the virus was not present in the urine after renal failure on day 14. Stool samples obtained on days 12 and 16 contained the virus, with up to 1031 RNA copies per g (close to the lowest detection limit of the assay). One of two oronasal swabs obtained on day 16 were positive, but yielded little viral RNA (5370 copies per mL). No virus was detected in blood. The full virus genome was combined with four other available full genome sequences in a maximum likelihood phylogeny, correlating branch lengths with dates of isolation. The time of the common ancestor was halfway through 2011. Addition of novel genome data from an unlinked case treated 6 months previously in Essen, Germany, showed a clustering of viruses derived from Qatar and the United Arab Emirates. Interpretation We have provided the first complete viral load profile in a case of MERS-CoV infection. MERS-CoV might have shedding patterns that are different from those of severe acute respiratory syndrome and so might need alternative diagnostic approaches. Funding European Union; German Centre for Infection Research; German Research Council; and German Ministry for Education and Research.

Anamnese und klinischer Befund: Ein 50-jahriger Patient mit HIV-Infektion (Erstdiagnose vor > 20 Jahren) stellte sich aufgrund einer ausgepragten oralen Mukositis erstmals vor. Eine antiretrovirale Therapie (ART) mit Tenofovir, Emtricitabin und Raltegravir war 2 Monate zuvor eingeleitet worden. Opportunistische Infektionen waren bislang nicht aufgetreten; es bestanden keine weiteren Vorerkrankungen. Ausereuropaische Auslandsaufenthalte wurden verneint; im Sommer hielt sich der Patient mehrere Wochen in Spanien auf. Untersuchungen, Diagnose: Bei der korperlichen Untersuchung fiel eine deutliche Schwellung der Lippen und eine ausgepragte ulzerierende Mukositis auf. Der Patient klagte uber starke Schluckbeschwerden. Laborchemisch zeigten sich keine Auffalligkeiten. In einem Abstrich sowie einer Biopsie buccal wurden mikroskopisch Leishmanien nachgewiesen. Mittels PCR konnte die Diagnose einer mukokutanen Leishmaniose durch Leishmania-donovani-Komplex gestellt werden. Therapie und Verlauf: Der Patient wurde zunachst mit liposomalem Amphotericin B (1 mg/kg KG) uber 21 Tage behandelt. Aufgrund der Immunsuppression wurde eine Erhaltungstherapie (liposomales Amphotericin B, 3 mg/kg KG alle 3 Wochen) durchgefuhrt. Dennoch kam es 4 Monate nach der Erstmanifestation zu einem klinischen Rezidiv mit kulturellem Nachweis von Leishmanien aus einer Mundschleimhautbiopsie. Nach einem weiteren 21-tagigen Therapiezyklus mit liposomalem Amphotericin B (3 mg/kg KG) und gleichzeitiger Gabe von Miltefosin (150 mg/d) ging die Mukositis vollstandig zuruck. Seither wird eine Erhaltungstherapie mit Amphotericin B (3 mg/kg KG) als Einmalgabe alle 3 Wochen durchgefuhrt. Die ART wurde unmittelbar nach Beendigung der Rezidivtherapie aufgrund erhohter Nierenretentionswerte auf Abacavir, Lamivudin und Raltegravir umgestellt. Der klinische Zustand ist seither stabil, weitere opportunistische Erkrankungen manifestierten sich nicht. Die CD4 Zellen betrugen zuletzt 456/µl bei einer HI-Viruslast von 340 Kopien/ml. Folgerung: Leishmanien konnen bei schlechter Immunlage lebenslang im Korper persistieren und reaktiviert werden. Daher ist die Leishmaniose auch eine ernstzunehmende Infektion bei Patienten mit HIV-Infektion. Speziell bei Immunsupprimierten konnen atypische klinische Manifestationen einer Leishmaniose auftreten. Bei HIV-Patienten ist die Therapie der Leishmaniose erschwert, eine Erhaltungstherapie (im Anschluss an die Standardtherapie) bei Helferzellen

Das Kaposi-Sarkom gehort zu den AIDS definierenden Erkrankungen. Oft ist primar die Haut betroffen, aber auch ein viszeraler Befall ist moglich. Zudem kann es rasch progredieren, daher ist eine adaquate Therapie essenziell.

HISTORY AND CLINICAL FINDINGS A 71-year-old woman had suffered for 6 weeks from fatigue, dry cough and fever. Five years previously breast cancer had been diagnosed and had been successfully treated with subtotal mastectomy and postoperative radiotherapy, as well as aromatase inhibitor until shortly before the present admission. There was no history of travel to tropical countries, but during the last summer she had spent two weeks in Northern Italy. [corrected] INVESTIGATIONS On admission the body temperature was 38,5 C with a mild tachycardia (108/min). Laboratory findings revealed a pancytopenia and slightly elevated liver enzymes. The ultrasound showed a hepatosplenomegaly. The investigation of the bone marrow showed a great amount of parasitic forms due to visceral leishmaniasis [corrected] TREATMENT, COURSE AND DIAGNOSIS: Treatment with liposomal amphotericin B brought about rapid improvement, the dry cough subsided and the laboratory results became normal. CONCLUSION Pancytopenia, fever, dry cough and hepatosplenomegaly after travelling to Mediterranean countries should raise suspicion of visceral leishmaniasis. This diagnosis is confirmed by direct detection of the parasite in the bone marrow. Administration of liposomal amphotericin B is efficacious and safe, bringing about full recovery in up to 90% of cases.

Ein 24-jahriger, HIV-positiver Patient wurde wegen progredienter Zephalgien stationar aufgenommen. Bei Aufnahme wurde ein adaquat orientierter Patient mit starksten holozephalen Kopfschmerzen, Ubelkeit und Erbrechen sowie diskretem Meningismus ohne neurologische Ausfalle gesehen. In der Lumbalpunktion konnten Kryptokokken direkt nachgewiesen werden. Der Patient wurde mit einer Dreifachkombination aus Amphotericin B, Flucytosin und Fluconazol behandelt, und zeitnah wurde eine antiretrovirale Therapie (ART) bei schwerer Immundefizienz begonnen. Der Allgemeinzustand besserte sich kontinuierlich, Kryptokokken waren nicht mehr nachweisbar und es wurde eine Erhaltungstherapie mit Fluco nazol durchgefuhrt. Etwa 2 Monate spater traten wieder starkste Kopfschmerzen auf. In der Liquorpunktion wurden erneut massenhaft Kryptokokken nachgewiesen. Die Resistenztestung der Kryptokokken ergab eine intermediare Resistenz gegenuber Fluconazol. Daraufhin wurde Fluconazol durch Voriconazol ersetzt. Hierunter war der Patient zunachst anhaltend beschwerdefrei. 8 Monate nach Beginn der ART kam es erneut zu massiven Kopfschmerzen und Erbrechen. Magnetresonanztomographisch war ein diskretes Hirnodem nachweisbar. Hinweise auf eine opportunistische Infektion oder ein Lymphom ergaben sich nicht; wegen des daher vermuteten Immunrekonstitutionssyndroms (IRIS) wurden Kortikosteroide appliziert. Hierunter kam es rasch zu einem volligen Sistieren samtlicher Beschwerden. Der Patient ist seither (19 Monate nach Erstdiagnose) beschwerdefrei. Die Kryptokokkenmeningoenzephalitis gehort zu den HIV-assoziierten Erkrankungen. Therapeutisch sollte eine antimykotische Kombinationstherapie durchgefuhrt werden. Allerdings muss auch bei Kryptokokken an Resistenzen gedacht werden. Wie bei anderen Infektionen kann es auch bei einer Kryptokokkenmeningoenzephalitis zu einem IRIS kommen.

We report 15 imported louse-borne relapsing fever (LBRF) cases in refugees in Bavaria, Germany. One patient died. Epidemiological findings confirmed that all were young males from the Horn of Africa (12 from Somalia), who had similar migration routes converging in Sudan continuing through Libya and Italy. The majority likely acquired their infection during migration. Healthcare workers should be aware of LBRF in refugees passing through north Africa to ensure correct treatment and preventive measures.

History and clinical findings A 49-year-old travel guide fell ill during his return from a 6-week-stay in Vietnam, Myanmar and Thailand. He developed high fever and severe headache. On admission, the body temperature was at 39.5 degrees C with relative bradycardia. A black, crusted skin lesion of approximately 5 mm diameter was noted on the chest wall and was interpreted as an insect bite. Investigations CRP and liver enzymes were elevated. Total leucocyte count was normal but the differential count showed a left shift and aneosinophilia. Imaging procedures revealed splenomegaly and small pleural effusions on both sides. Treatment and course The patient was treated with a parenteral quinolone based on the initial suspicion of typhoid fever. Failure of this treatment and negative blood cultures raised concerns about the possibility of Tsutsugamushi fever, based on travel history and a re-evaluation of the skin lesion as an eschar. Tsutsugamushi fever was suspected on epidemiological and clinical grounds and was confirmed by the detection of specific IgM to Orienta tsutsugamushi and by seroconversion of IgG antibodies during follow-up. Even before immunodiagnostic confirmation was available, a course of doxycycline was started. This led to rapid improvement of the patient's condition. Conclusion In febrile travellers returning from Southeast Asia, Tsutsugamushi fever has to be considered in the differential diagnosis. The causative agent, Orienta tsutsugamushi is transmitted by larvae of trombiculid mites (chiggers). Leading symptoms are fever continua, cephalgia, and a primary lesion (eschar) at the site of cutaneous inoculation. The Eschar is easily overlooked and has to be searched carefully. Diagnosis is confirmed by the detection of specific antibodies. However, serology may be negative in the beginning. Therefore, treatment with doxycycline should be initiated on clinical grounds.

A 24-year-old HIV-positive patient was admitted to hospital on account of increasing headache.On admission, a patient with severe headache, nausea and vomiting but without neurologic deficiencies was seen. The diagnosis of a cryptococcal meningoencephalitis could be confirmed by direct detection of cryptococci in the liquor.The patient was treated with a combination of fluconazole, flucytosine and amphotericin B, and an antiretroviral therapy (ART) was started on account of the severe immunodeficiency. The patient improved during the following weeks, and fluconazole was administered as maintainance therapy. About 2 months later, the patient presented again with severe headache. On lumbar puncture, a great amount of cryptococci could be detected, and the antimycotic combination therapy was restarted. An antimycotic testing of the cryptococci revealed a partial resistance to fluconazole. Therefore, fluconazole was replaced by voriconazole which has been continued ever since. Cryptococci could not be detected on further investigations of the liquor. The patient's condition worsened again 8 months after initiation of the ART. MR scan showed a slight cerebral edema. There was no hint of an opportunistic infection nor of a lymphoma. The complaints were supposed to be due to an immune restoration inflammatory syndrome (IRIS), and administration of high steroid dosages was started. The complaints resolved within 48 h, and the patient's condition has been stable ever since (19 months).Cryptococcal meningoencephalitis is an opportunistic infection in AIDS. Therapeutically, various regimens containing two to three different antimycotic drugs show good efficacy but resistance to antimycotics has to be considered. As in other HIV associated infections, an IRIS has to be taken into account.

During the last two decades human infections with Plasmodium knowlesi are increasingly diagnosed in South East Asia and have also been reported in travellers. A severe case of imported P. knowlesi infection in a 73-year old German is presented, who had been travelling through Myanmar and Thailand for three weeks. Microscopy showed a parasitaemia of 3% and different parasite stages including band-forms resembling Plasmodium malariae. Due to the clinical picture of severe malaria and the microscopical aspect (combination of parasites resembling P. malariae and Plasmodium falciparum), P. knowlesi was suspected. The patient was treated with intravenous quinine; he was put on mechanical ventilation and catecholamines due to cardiorespiratory failure. Parasitaemia was cleared rapidly but renal function deteriorated resulting in intermittent haemodialysis. The patient was hospitalized for six weeks but he recovered completely without any physical sequelae. Plasmodium knowlesi mono-infection was confirmed by molecular methods later on. Plasmodium knowlesi infection has to be taken into account in feverish travellers returning from Thailand/Myanmar. Moreover this species can cause life-threatening or even lethal complications. Accordingly severe P. knowlesi infection should be treated like severe P. falciparum infections.