[COVID-19: epidemiology and mutations : An update]. / COVID-19: Epidemiologie und Mutationen : Ein Update.

Mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can enhance the spread and the infectiousness and decrease the protective effect of antibodies present after infection, vaccination or antibody treatment. The alpha variant (B.1.1.7), first seen in Kent/United Kingdom, has increased the R­value and therefore the infectiousness by 75%; however, the effectiveness of the vaccines against SARS-CoV­2 available in Germany seems to be only slightly impaired by these mutations. In the case of the beta variant (B.1.351), first described in South Africa, the neutralization ability of antibodies towards SARS-CoV­2 is decreased. The monoclonal antibodies bamlanivimab and etesivimab, which are used therapeutically, are ineffective. The AstraZeneca vaccine offers almost no protection against mild or moderate disease caused by the beta variant. The gamma variant (P.1 or B.1.1.28.1), which was first found in Brazil, is probably 1.7-2.6 times more transmissible than previous virus strains circulating in Brazil. In addition to the infectiousness, the mortality risk of the gamma variant also seems to be increased between 1.2 and 1.9-fold in adults and between 5 and 8-fold in young persons. The delta variant (B.1.617), first described in India, is now dominant in most countries. It is 50% more infectious than the alpha variant, and the protective effect of vaccinations against symptomatic disease can be decreased (Biontech: delta variant 88%, alpha variant 93.7%; AstraZeneca: delta variant 67%, alpha variant 74.5%). Furthermore, the course of the disease with the delta variant is often more severe than with the wild type. Disease courses with the delta variant are less severe in vaccinated than in nonvaccinated persons, and fatal outcomes are substantially rarer. A high vaccination rate is essential in order to approach herd immunity and to bring the pandemic under control. Even where the protective effect towards mild or moderate disease is decreased, as a rule, vaccination still offers excellent protection against life-threatening and fatal disease courses.

[COVID-19: epidemiology and clinical facts]. / COVID-19: Epidemiologische und klinische Fakten.

Until July 31, 2020, about 17.6 million SARS-CoV­2 infections and 680,000 deaths from COVID-19 were reported. SARS-CoV­2 is most likely transmitted by droplets and probably by aerosols. Patients become infectious 2-3 days before the onset of symptoms, and persons with asymptomatic infections are also infectious. COVID-19 affects the upper respiratory tract, lungs (pneumonia, acute respiratory distress syndrome [ARDS]), heart, liver, gastrointestinal tract, and other organs. SARS-CoV­2 uses ACE2 a receptor to enter host cells. Vasculitis, endothelial damage, thromboembolic events and organ failure are accompanied by a massive cytokine response. Elderly people and those with pre-existing diseases are particularly vulnerable. An efficient antiviral therapy is not yet available. Severely ill patients may benefit from dexamethasone and early treatment of complications. Candidate vaccines are currently being tested in clinical studies.

Crimean-Congo Hemorrhagic Fever, Kosovo, 2013-2016.

During 2013-2016, a total of 32 patients were treated for Crimean-Congo hemorrhagic fever in Prishtina, Kosovo; 11 died. In the 11 patients who died, findings included viral loads >1 × 108.5/mL, lactate dehydrogenase >2,700 U/mL, bleeding, and impaired consciousness. Ribavirin therapy had no noticeable effect in this small patient sample.

Tuberculosis-associated hemophagocytic lymphohistiocytosis with subsequent unmasking cryptococcal immune reconstitution inflammatory syndrome (IRIS) in an HIV-negative man.

A 22-year-old HIV-negative man from Ghana was diagnosed with severe hemophagocytic lymphohistiocytosis (HLH) induced by multiorgan tuberculosis with peritoneal, hepatic, pericardial, myocardial, pleural, pulmonary, and bone manifestation. His body mass index was 12.9 m2/kg. Bioptic material of a peritoneal biopsy grew M. tuberculosis, sensitive to all first-line antituberculous drugs. HLH resolved with antituberculous therapy, without additional anti-inflammatory therapy being given. The initial CT scan of his brain was normal. After 5 months of antituberculous treatment, he developed a paralysis of the left arm. A cerebral MRT showed ring-enhanced lesions. Blood cultures and lumbar puncture revealed Cryptococcus neoformans var. grubi. The HIV test was repeatedly negative. Antituberculous treatment was continued for a total of 9 months, and additional treatment with antifungal therapy was established. He recovered fully after 14 months of antifungal treatment.

Activated protein C protects vascular endothelial cells from apoptosis in malaria and in sepsis.

OBJECTIVE: In malaria and sepsis, apoptotic endothelial damage is preventable in vitro by antioxidants and protease inhibitors. Activated protein C, which has anti-apoptotic effects, improves survival in sepsis. Therefore, we studied whether activated protein C prevents endothelial cell apoptosis, induced by serum from patients with malaria or sepsis. METHODS: Endothelial cells were incubated with patient sera (Plasmodium falciparum malaria, Escherichia coli sepsis, Staphylococcus aureus sepsis) or culture supernatants of the respective organisms, with or without neutrophils. Activated protein C was used to reduce endothelial cell apoptosis in vitro. The proportion of apoptotic endothelial cells was determined by TUNEL staining. RESULTS: The apoptosis-inducing effect of patient sera or culture supernatants (P. falciparum, E. coli, S. aureus) on endothelial cells was augmented by neutrophils and reduced by activated protein C in the presence of neutrophils. Pre-incubating either endothelial cells or neutrophils with activated protein C also reduced the endothelial cell apoptosis rate. The pro-apoptotic effect of P. falciparum supernatant was reduced by pan-caspase inhibitor and caspase 8 inhibitor, but not by caspase 9 inhibitor. The pro-apoptotic effect of E. coli and S. aureus supernatants was also reduced by caspase 9 inhibitor. CONCLUSIONS: Activated protein C protects vascular endothelial cells from apoptosis triggered by patient sera or culture supernatants in combination with neutrophils. It seems to act both on neutrophils and on endothelial cells. Activated protein C blocks caspase-8-dependent apoptosis, which accounts for endothelial damage in sepsis and malaria. Therefore, activated protein C might offer clinical benefit not only in sepsis but also in malaria.

Immunotherapy and vaccination against infectious diseases.

Due to the overuse of antibiotics, infections, in particular those caused by multidrug-resistant bacteria, are becoming more and more frequent. Despite the worldwide introduction of antibiotic therapy, vaccines and constant improvements in hygiene, the burden of multidrug-resistant bacterial infections is increasing and is expected to rise in the future. The development of monoclonal therapeutic antibodies and specific immunomodulatory drugs represent new treatment options in the fight against infectious diseases. This article provides a brief overview of recent advances in immunomodulatory therapy and other strategies in the treatment of infectious disease.

[Screening of Mothers in a COVID-19 Low-Prevalence Region: Determination of SARS-CoV-2 Antibodies in 401 Mothers from Rostock by ELISA and Confirmation by Immunofluorescence]. / Mütter-Screening in einem COVID-19-Niedrig-Pandemiegebiet: Bestimmung SARS-CoV-2-spezifischer Antikörper bei 401 Rostocker Müttern mittels ELISA und Immunfluoreszenz-Bestätigungstest.

BACKGROUND: In children, the infection with SARS-CoV-2, the cause of COVID-19, tends to be clinically inapparent more often or less severe than in adults. The spread of this infection from children poses a danger to vulnerable adults. Therefore, child care institutions and schools currently are widely closed. METHODS: Since the status of infection tends to be congruent in mothers and their children, we tested 401 mothers of children between 1 and 10 years in the city of Rostock (State of Mecklenburg-Westpomerania, northeast of Germany), for the presence of RNA of SARS-CoV-2 in throat swabs, and of antibodies against SARS-CoV-2 in serum. RESULTS: In none of the mothers tested, RNA of this virus was detected in the throat swab. In the ELISA test, IgG antibodies were positive in one serum sample, IgA antibodies were positive in 11, and borderline in 3 serum samples. All 401 sera were negative in the indirect immunofluorescence test (IIFT) with FITC-labeled IgG, IgA, und IgM antibodies. CONCLUSION: At the time of this study, neither SARS-CoV-2 RNA, nor specific antibodies against SARS-CoV-2 were detectable in the mothers tested in Rostock.

Malaria and bacterial sepsis: similar mechanisms of endothelial apoptosis and its prevention in vitro.

OBJECTIVE AND DESIGN: Apoptotic endothelial damage contributes to multiorgan failure in Plasmodium falciparum malaria and in sepsis. In malaria, endothelial apoptosis is amplified by neutrophils and their secretory products, and reduced by inhibitors of neutrophil-derived substances in vitro. We compared the mechanisms of endothelial apoptosis in malaria and in sepsis, using the human umbilical vein endothelial cell as a model. INTERVENTIONS: Endothelial cells were incubated with patient sera (P. falciparum malaria, Escherichia coli sepsis, Staphylococcus aureus sepsis) or culture supernatants of the respective organisms, with or without neutrophils. Ascorbic acid or ulinastatin was used to neutralize reactive oxygen species or elastase secreted by neutrophils. Transwell sieve inserts or antibodies against leukocyte function antigen 1 or intercellular adhesion molecule 1 was used to study the effect of direct interaction between neutrophils and endothelial cells. The rate of apoptotic endothelial cells was determined by TUNEL and annexin staining. MEASUREMENTS AND MAIN RESULTS: Incubation of endothelial cells with patient sera or culture supernatants (P. falciparum, E. coli, S. aureus) lead to higher apoptosis rates, compared with incubation with control sera or control supernatants. Addition of neutrophils augmented the apoptosis rate further. Addition of ascorbic acid or ulinastatin reduced endothelial apoptosis in the presence of neutrophils. Separation of neutrophils from endothelial cells with Transwell sieve inserts, or addition of anti-leukocyte function antigen-1 antibodies also reduced endothelial cell apoptosis. However, addition of anti-intercellular adhesion molecule-1 antibodies restored high apoptosis rates that had been reduced by Transwell inserts. CONCLUSIONS: These in vitro results show how neutrophils can contribute to endothelial damage in malaria and in sepsis, both by their secretory products and by binding to intercellular adhesion molecule-1 on endothelial cells. The presence of similar pathomechanisms suggests that similar antiapoptotic strategies may offer potential benefit in malaria and in sepsis.

Effect of Tenofovor Diproxil Fumarate on Renal Function and Urinalysis Abnormalities in HIV-Infected Cameroonian Adults.

In Sub-Saharan Africa, the prevalence of HIV-associated kidney diseases is as high as 53.3%. Combined antiretroviral treatment (cART), especially tenofovir disoproxil fumarate (TDF), is known to be nephrotoxic. We undertook this cross-sectional study conducted in 2015 at the Regional Hospital Limbe in the Southwest Region of Cameroon to determine the prevalence of renal dysfunction and its correlates among treatment-experienced HIV-infected patients on TDF and treatment-naïve patients. In April 2016, a follow-up was performed on those who had been treatment-naïve and were started on cART after enrolment in the study. We compared 119 patients on TDF-containing regimens with 47 treatment-naïve patients. Proteinuria was significantly more prevalent, and creatinine was significantly higher among treatment-naïve patients than among those on treatment (52.2% versus 26.1%; P = 0.003 and P = 0.009, respectively). The proportion of patients with an estimated glomerular filtration rate (eGFR) < 60 mL/minute was significantly higher among treatment-naïve patients than among those on TDF treatment (40.4% versus 24.4%; P = 0.041). Treatment-naïve patients displayed an improvement in creatinine levels and eGFR after 6 months of treatment. To the best of our knowledge, this is the first study to investigate the impact of TDF on renal parameters in Cameroon. TDF appears to be safe and does not appear to be a significant cause of renal impairment. However, renal parameters should be monitored regularly, as recommended by the guidelines.

Human cowpox virus infection acquired from a circus elephant in Germany.

A 40-year-old Asian circus elephant developed mouth and trunk ulcers. Three weeks later, her 19-year-old animal warden noticed a vesicle on his forearm, evolving into a scab. Identical cowpox strains were isolated from lesions of the elephant and the warden. Cowpox virus could no longer be isolated after the scab disappeared, but PCR still revealed orthopox DNA. Healing was complete seven weeks later, leaving a 1 cm scar.