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Article ; Online: Intravenous immunoglobulin therapy for COVID-19 in immunocompromised patients: a retrospective cohort study.

Gröning, Remigius / Walde, Jonatan / Ahlm, Clas / Forsell, Mattias Ne / Normark, Johan / Rasmuson, Johan

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases

2024 , Page(s) 107046

Abstract: Objectives: To investigate the effectiveness of intravenous immunoglobulin (IVIG) as treatment for COVID-19 in immunocompromised patients.: Methods: This retrospective study investigated outcomes for immunocompromised, vaccine non-responsive, ... ...

Abstract	Objectives: To investigate the effectiveness of intravenous immunoglobulin (IVIG) as treatment for COVID-19 in immunocompromised patients. Methods: This retrospective study investigated outcomes for immunocompromised, vaccine non-responsive, patients that between September 2022 and April 2023 received IVIG as treatment for COVID-19 in the region of Västerbotten, Sweden. We analyzed clinical data, viral load, and anti-SARS-CoV-2 IgG binding and neutralization levels of patient serum samples and IVIG production batches. Primary and secondary outcomes were clinical cure and viral clearance, respectively. Results: Sixteen patients were analyzed. After a median COVID-19 duration of four weeks, a median 60g IVIG infusion increased SARS-CoV-2 binding and neutralizing antibody levels, with broad in vitro activity against tested variants. The treatment resulted in abrogation of viremia in all patients and general improvement in 15 survivors that all met the primary endpoint. Thirteen patients met the secondary endpoint at follow-up after a median of four months. Two subjects with persistent SARS-CoV-2 carriage relapsed but were successfully retreated with IVIG. Conclusions: Antibodies in IVIG efficiently neutralized several SARS-CoV-2 variants. Treatment with IVIG was associated with clinical cure and viral clearance in immunocompromised patients. Our data suggests that IVIG could be a novel treatment alternative for COVID-19 for this patient category.
Language	English
Publishing date	2024-04-12
Publishing country	Canada
Document type	Journal Article
ZDB-ID	1331197-9
ISSN	1878-3511 ; 1201-9712
ISSN (online)	1878-3511
ISSN	1201-9712
DOI	10.1016/j.ijid.2024.107046
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Article: Mosquito-borne viruses causing human disease in Fennoscandia-Past, current, and future perspectives.

Wilkman, Lukas / Ahlm, Clas / Evander, Magnus / Lwande, Olivia Wesula

Frontiers in medicine

2023 Volume 10, Page(s) 1152070

Abstract: Five different mosquito-borne viruses (moboviruses) significant to human disease are known to be endemic to Fennoscandia (Sindbis virus, Inkoo virus, Tahyna virus, Chatanga virus, and Batai virus). However, the incidence of mosquito-borne virus ... ...

Abstract	Five different mosquito-borne viruses (moboviruses) significant to human disease are known to be endemic to Fennoscandia (Sindbis virus, Inkoo virus, Tahyna virus, Chatanga virus, and Batai virus). However, the incidence of mosquito-borne virus infections in Fennoscandia is unknown, largely due to underdiagnosing and lack of surveillance efforts. The Fennoscandian moboviruses are difficult to prevent due to their method of transmission, and often difficult to diagnose due to a lack of clear case definition criteria. Thus, many cases are likely to be mis-diagnosed, or even not diagnosed at all. Significant long-term effects, often in the form of malaise, rashes, and arthralgia have been found for some of these infections. Research into mobovirus disease is ongoing, though mainly focused on a few pathogens, with many others neglected. With moboviruses found as far north as the 69
Language	English
Publishing date	2023-03-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2023.1152070
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Article ; Online: Immune response to SARS-CoV-2 mRNA vaccination in multiple sclerosis patients after rituximab treatment interruption.

Gröning, Remigius / Dernstedt, Andy / Ahlm, Clas / Normark, Johan / Sundström, Peter / Forsell, Mattias N E

Frontiers in immunology

2023 Volume 14, Page(s) 1219560

Abstract: Peripheral B cell ... ...

Abstract	Peripheral B cell depletion
MeSH term(s)	Humans ; BNT162 Vaccine ; Rituximab/therapeutic use ; SARS-CoV-2 ; Multiple Sclerosis/drug therapy ; COVID-19/prevention & control ; Vaccination ; Antibodies ; Immunity ; RNA, Messenger
Chemical Substances	BNT162 Vaccine ; Rituximab (4F4X42SYQ6) ; Antibodies ; RNA, Messenger
Language	English
Publishing date	2023-07-27
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1219560
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Article ; Online: Vector competence of Anopheles stephensi for O'nyong-nyong virus: a risk for global virus spread.

Mutsaers, Maud / Engdahl, Cecilia Springer / Wilkman, Lukas / Ahlm, Clas / Evander, Magnus / Lwande, Olivia Wesula

Parasites & vectors

2023 Volume 16, Issue 1, Page(s) 133

Abstract: Background: O'nyong-nyong virus (ONNV) is a mosquito-borne alphavirus causing sporadic outbreaks of febrile illness with rash and polyarthralgia. Up to now, ONNV has been restricted to Africa and only two competent vectors have been found, Anopheles ... ...

Abstract	Background: O'nyong-nyong virus (ONNV) is a mosquito-borne alphavirus causing sporadic outbreaks of febrile illness with rash and polyarthralgia. Up to now, ONNV has been restricted to Africa and only two competent vectors have been found, Anopheles gambiae and An. funestus, which are also known malaria vectors. With globalization and invasive mosquito species migrating to ONNV endemic areas, there is a possible risk of introduction of the virus to other countries and continents. Anopheles stephensi, is closely related to An. gambiae and one of the invasive mosquito species of Asian origin that is now present in the Horn of Africa and spreading further east. We hypothesize that An. stephensi, a known primary urban malaria vector, may also serve as a new possible vector for ONNV. Methods: One-week-old female adult An. stephensi were exposed to ONNV-infected blood, and the vector competence for ONNV, i.e. infection rates (IRs), dissemination rates (DRs), transmission rates (TRs), dissemination efficiency (DEs) and transmission efficiency (TEs), were evaluated. Infection (IRs), dissemination efficiency (DEs) and transmission efficiency (TEs) were determined. Detection of ONNV RNA was analysed by RT-qPCR in the thorax and abdomen, head, wings, legs and saliva of the infected mosquitoes at four different time points, day 7, 14, 21 and 28 after blood meal. Infectious virus in saliva was assessed by infection of Vero B4 cells. Results: The mean mortality across all sampling times was 27.3% (95 confidence interval [CI] 14.7-44.2%). The mean rate of infection across all sampling periods was 89.5% (95% CI 70.6-95.9). The mean dissemination rate across sampling intervals was 43.4% (95% CI 24.3-64.2%). The mean TR and TE across all mosquito sampling time intervals were 65.3 (95% CI 28.6-93.5) and 74.6 (95% CI 52.1-89.4). The IR was 100%, 79.3%, 78.6% and 100% respectively at 7, 14, 21 and 28 dpi. The DR was the highest at 7 dpi with 76.0%, followed by 28 dpi at 57.1%, 21 dpi at 27.3% and 14 dpi at the lowest DR of 13.04%. DE was 76%, 13.8%, 25%, 57.1% and TR was 79%, 50%, 57.1% and 75% at 7, 14, 21 and 28 dpi respectively. The TE was the highest at 28 dpi, with a proportion of 85.7%. For 7, 14 and 21 dpi the transmission efficiency was 72.0%, 65.5% and 75.0% respectively. Conclusion: Anopheles stephensi is a competent vector for ONNV and being an invasive species spreading to different parts of the world will likely spread the virus to other regions.
MeSH term(s)	Animals ; Female ; Humans ; O'nyong-nyong Virus ; Anopheles/genetics ; Mosquito Vectors ; Malaria/epidemiology ; Alphavirus/genetics
Language	English
Publishing date	2023-04-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2409480-8
ISSN	1756-3305 ; 1756-3305
ISSN (online)	1756-3305
ISSN	1756-3305
DOI	10.1186/s13071-023-05725-0
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Article ; Online: Public health determinants of child malaria mortality: a surveillance study within Siaya County, Western Kenya.

Hollowell, Thomas / Sewe, Maquins Odhiambo / Rocklöv, Joacim / Obor, David / Odhiambo, Frank / Ahlm, Clas

Malaria journal

2023 Volume 22, Issue 1, Page(s) 65

Abstract: Background: Malaria deaths among children have been declining worldwide during the last two decades. Despite preventive, epidemiologic and therapy-development work, mortality rate decline has stagnated in western Kenya resulting in persistently high ... ...

Abstract	Background: Malaria deaths among children have been declining worldwide during the last two decades. Despite preventive, epidemiologic and therapy-development work, mortality rate decline has stagnated in western Kenya resulting in persistently high child malaria morbidity and mortality. The aim of this study was to identify public health determinants influencing the high burden of malaria deaths among children in this region. Methods: A total of 221,929 children, 111,488 females and 110,441 males, under the age of 5 years were enrolled in the Kenya Medical Research Institute/Center for Disease Control Health and Demographic Surveillance System (KEMRI/CDC HDSS) study area in Siaya County during the period 2003-2013. Cause of death was determined by use of verbal autopsy. Age-specific mortality rates were computed, and cox proportional hazard regression was used to model time to malaria death controlling for the socio-demographic factors. A variety of demographic, social and epidemiologic factors were examined. Results: In total 8,696 (3.9%) children died during the study period. Malaria was the most prevalent cause of death and constituted 33.2% of all causes of death, followed by acute respiratory infections (26.7%) and HIV/AIDS related deaths (18.6%). There was a marked decrease in overall mortality rate from 2003 to 2013, except for a spike in the rates in 2008. The hazard of death differed between age groups with the youngest having the highest hazard of death HR 6.07 (95% CI 5.10-7.22). Overall, the risk attenuated with age and mortality risks were limited beyond 4 years of age. Longer distance to healthcare HR of 1.44 (95% CI 1.29-1.60), l ow maternal education HR 3.91 (95% CI 1.86-8.22), and low socioeconomic status HR 1.44 (95% CI 1.26-1.64) were all significantly associated with increased hazard of malaria death among children. Conclusions: While child mortality due to malaria in the study area in Western Kenya, has been decreasing, a final step toward significant risk reduction is yet to be accomplished. This study highlights residual proximal determinants of risk which can further inform preventive actions.
MeSH term(s)	Male ; Female ; Humans ; Child ; Infant ; Child, Preschool ; Child Mortality ; Cause of Death ; Kenya/epidemiology ; Malaria/epidemiology ; Population Surveillance
Language	English
Publishing date	2023-02-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2091229-8
ISSN	1475-2875 ; 1475-2875
ISSN (online)	1475-2875
ISSN	1475-2875
DOI	10.1186/s12936-023-04502-9
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Article: Human herpes virus type-6 is associated with central nervous system infections in children in Sudan.

Abdelrahim, Nada A / Mohamed, Nahla / Evander, Magnus / Ahlm, Clas / Fadl-Elmula, Imad M

African journal of laboratory medicine

2022 Volume 11, Issue 1, Page(s) 1718

Abstract: Background: Human herpes virus type-6 (HHV-6) is increasingly recognised as a febrile agent in children. However, less is known in sub-Saharan African countries, including Sudan.: Objective: We investigated the involvement of HHV-6 in paediatric ... ...

Abstract	Background: Human herpes virus type-6 (HHV-6) is increasingly recognised as a febrile agent in children. However, less is known in sub-Saharan African countries, including Sudan. Objective: We investigated the involvement of HHV-6 in paediatric central nervous system (CNS) infections in Khartoum, Sudan. Methods: Febrile patients aged up to 15 years with suspected CNS infections at Omdurman Hospital for Children from 01 December 2009 to 01 August 2010 were included. Viral DNA was extracted from leftover cerebrospinal fluid (CSF) specimens and quantitatively amplified by real-time polymerase chain reaction (PCR) at Umeå University in Sweden. Results: Of 503 CSF specimens, 13 (2.6%) were positive for HHV-6 (33.0% [13/40 of cases with proven infectious meningitis]). The median thermal cycle threshold for all HHV-6-positive specimens was 38 (range: 31.9-40.8). The median number of virus copies was 281.3/PCR run (1 × 10 Conclusion: Among children in Sudan with CNS infections, HHV-6 is common. Studies on the existence and spread of HHV-6 chromosomal integration in this population are needed.
Language	English
Publishing date	2022-09-22
Publishing country	South Africa
Document type	Journal Article
ZDB-ID	2708535-1
ISSN	2225-2010 ; 2225-2002
ISSN (online)	2225-2010
ISSN	2225-2002
DOI	10.4102/ajlm.v11i1.1718
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Article ; Online: Viral meningitis in Sudanese children: Differentiation, etiology and review of literature.

Abdelrahim, Nada Abdelghani / Mohammed, Nahla / Evander, Magnus / Ahlm, Clas / Fadl-Elmula, Imad Mohammed

Medicine

2022 Volume 101, Issue 46, Page(s) e31588

Abstract: Diagnosis of viral meningitis (VM) is uncommon practice in Sudan and there is no local viral etiological map. We therefore intended to differentiate VM using standardized clinical codes and determine the involvement of herpes simplex virus types-1 and 2 ( ...

Abstract	Diagnosis of viral meningitis (VM) is uncommon practice in Sudan and there is no local viral etiological map. We therefore intended to differentiate VM using standardized clinical codes and determine the involvement of herpes simplex virus types-1 and 2 (HSV-1/2), varicella zoster virus, non-polio human enteroviruses (HEVs), and human parechoviruses in meningeal infections in children in Sudan. This is a cross-sectional hospital-based study. Viral meningitis was differentiated in 503 suspected febrile attendee of Omdurman Hospital for Children following the criteria listed in the Clinical Case Definition for Aseptic/Viral Meningitis. Patients were children age 0 to 15 years. Viral nucleic acids (DNA/RNA) were extracted from cerebrospinal fluid (CSF) specimens using QIAamp® UltraSens Virus Technology. Complementary DNA was prepared from viral RNA using GoScriptTM Reverse Transcription System. Viral nucleic acids were amplified and detected using quantitative TaqMan® Real-Time and conventional polymerase chain reactions (PCRs). Hospital diagnosis of VM was assigned to 0%, when clinical codes were applied; we considered 3.2% as having VM among the total study population and as 40% among those with proven infectious meningitis. Two (0.4%) out of total 503 CSF specimens were positive for HSV-1; Ct values were 37.05 and 39.10 and virus copies were 652/PCR run (261 × 103/mL CSF) and 123/PCR run (49.3 × 103/mL CSF), respectively. Other 2 (0.4%) CSF specimens were positive for non-polio HEVs; Ct values were 37.70 and 38.30, and the approximate virus copies were 5E2/PCR run (~2E5/mL CSF) and 2E2/PCR run (~8E4/mL CSF), respectively. No genetic materials were detected for HSV-2, varicella zoster virus, and human parechoviruses. The diagnosis of VM was never assigned by the hospital despite fulfilling the clinical case definition. Virus detection rate was 10% among cases with proven infectious meningitis. Detected viruses were HSV-1 and non-polio HEVs. Positive virus PCRs in CSFs with normal cellular counts were seen.
MeSH term(s)	Humans ; Child ; Infant, Newborn ; Infant ; Child, Preschool ; Adolescent ; Cross-Sectional Studies ; Meningitis, Viral/diagnosis ; Meningitis, Viral/epidemiology ; Herpesvirus 2, Human ; Herpesvirus 1, Human ; Herpesvirus 3, Human ; Enterovirus ; Viruses ; Parechovirus ; Nucleic Acids
Chemical Substances	Nucleic Acids
Language	English
Publishing date	2022-11-18
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	80184-7
ISSN	1536-5964 ; 0025-7974
ISSN (online)	1536-5964
ISSN	0025-7974
DOI	10.1097/MD.0000000000031588
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Article ; Online: Hantavirus in humans: a review of clinical aspects and management.

Vial, Pablo A / Ferrés, Marcela / Vial, Cecilia / Klingström, Jonas / Ahlm, Clas / López, René / Le Corre, Nicole / Mertz, Gregory J

The Lancet. Infectious diseases

2023 Volume 23, Issue 9, Page(s) e371–e382

Abstract: Hantavirus infections are part of the broad group of viral haemorrhagic fevers. They are also recognised as a distinct model of an emergent zoonotic infection with a global distribution. Many factors influence their epidemiology and transmission, such as ...

Abstract	Hantavirus infections are part of the broad group of viral haemorrhagic fevers. They are also recognised as a distinct model of an emergent zoonotic infection with a global distribution. Many factors influence their epidemiology and transmission, such as climate, environment, social development, ecology of rodent hosts, and human behaviour in endemic regions. Transmission to humans occurs by exposure to infected rodents in endemic areas; however, Andes hantavirus is unique in that it can be transmitted from person to person. As hantaviruses target endothelial cells, they can affect diverse organ systems; increased vascular permeability is central to pathogenesis. The main clinical syndromes associated with hantaviruses are haemorrhagic fever with renal syndrome (HFRS), which is endemic in Europe and Asia, and hantavirus cardiopulmonary syndrome (HCPS), which is endemic in the Americas. HCPS and HFRS are separate clinical entities, but they share several features and have many overlapping symptoms, signs, and pathogenic alterations. For HCPS in particular, clinical outcomes are highly associated with early clinical suspicion, access to rapid diagnostic testing or algorithms for presumptive diagnosis, and prompt transfer to a facility with critical care units. No specific effective antiviral treatment is available.
MeSH term(s)	Humans ; Hemorrhagic Fever with Renal Syndrome/diagnosis ; Hemorrhagic Fever with Renal Syndrome/epidemiology ; Hemorrhagic Fever with Renal Syndrome/therapy ; Orthohantavirus ; Endothelial Cells/pathology ; Hantavirus Pulmonary Syndrome/diagnosis ; Hantavirus Pulmonary Syndrome/drug therapy ; Hantavirus Pulmonary Syndrome/epidemiology ; Hantavirus Infections/diagnosis ; Hantavirus Infections/epidemiology ; Hantavirus Infections/therapy ; Communicable Diseases
Language	English
Publishing date	2023-04-24
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(23)00128-7
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Zs.A 5743: Show issues

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Article ; Online: Direct and indirect effects of Puumala hantavirus on platelet function.

Schrottmaier, Waltraud C / Schmuckenschlager, Anna / Thunberg, Therese / Wigren-Byström, Julia / Fors-Connolly, Anne-Marie / Assinger, Alice / Ahlm, Clas / Forsell, Mattias N E

Thrombosis research

2023 Volume 233, Page(s) 41–54

Abstract: Thrombocytopenia is a cardinal symptom of hantavirus-induced diseases including Puumala virus (PUUV)-induced hemorrhagic fever with renal syndrome (HFRS), which is associated with impaired platelet function, bleeding manifestations and augmented ... ...

Abstract	Thrombocytopenia is a cardinal symptom of hantavirus-induced diseases including Puumala virus (PUUV)-induced hemorrhagic fever with renal syndrome (HFRS), which is associated with impaired platelet function, bleeding manifestations and augmented thrombotic risk. However, the underlying mechanisms causing thrombocytopenia and platelet hypo-responsiveness are unknown. Thus, we investigated the direct and indirect impact of PUUV on platelet production, function and degradation. Analysis of PUUV-HFRS patient blood revealed that platelet hypo-responsiveness in PUUV infection was cell-intrinsic and accompanied by reduced platelet-leukocyte aggregates (PLAs) and upregulation of monocyte tissue factor (TF), whereas platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation was comparable to healthy controls. Plasma CXCL4 levels followed platelet count dynamics throughout disease course. PUUV activated both neutrophils and monocytes in vitro, but platelet desialylation, degranulation and GPIIb/IIIa activation as well as PLA formation and endothelial adhesion under flow remained unaltered in the presence of PUUV. Further, MEG-01 megakaryocytes infected with PUUV displayed unaltered polyploidization, expression of surface receptors and platelet production. However, infection of endothelial cells with PUUV significantly increased platelet sequestration. Our data thus demonstrate that although platelet production, activation or degradation are not directly modulated, PUUV indirectly fosters thrombocytopenia by sequestration of platelets to infected endothelium. Upregulation of immunothrombotic processes in PUUV-HFRS may further contribute to platelet dysfunction and consumption. Given the pathophysiologic similarities of hantavirus infections, our findings thus provide important insights into the mechanisms underlying thrombocytopenia and highlight immune-mediated coagulopathy as potential therapeutic target.
MeSH term(s)	Humans ; Puumala virus ; Hemorrhagic Fever with Renal Syndrome/diagnosis ; Hemorrhagic Fever with Renal Syndrome/therapy ; Endothelial Cells ; Orthohantavirus ; Thrombocytopenia
Language	English
Publishing date	2023-11-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	121852-9
ISSN	1879-2472 ; 0049-3848
ISSN (online)	1879-2472
ISSN	0049-3848
DOI	10.1016/j.thromres.2023.11.017
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Article ; Online: Hybrid capture-based next-generation sequencing of new and old world Orthohantavirus strains and wild-type Puumala isolates from humans and bank voles.

Rosenbaum, William / Bovinder Ylitalo, Erik / Castel, Guillaume / Sjödin, Andreas / Larsson, Pär / Wigren Byström, Julia / Forsell, Mattias N E / Ahlm, Clas / Pettersson, Lisa / Tuiskunen Bäck, Anne

Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology

2024 Volume 172, Page(s) 105672

Abstract: Orthohantaviruses, transmitted primarily by rodents, cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome in the Americas. These viruses, with documented human-to-human transmission, exhibit a wide case-fatality ...

Abstract	Orthohantaviruses, transmitted primarily by rodents, cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome in the Americas. These viruses, with documented human-to-human transmission, exhibit a wide case-fatality rate, 0.5-40 %, depending on the virus species, and no vaccine or effective treatment for severe Orthohantavirus infections exists. In Europe, the Puumala virus (PUUV), carried by the bank vole Myodes glareolus, causes a milder form of HFRS. Despite the reliance on serology and PCR for diagnosis, the three genomic segments of Swedish wild-type PUUV have yet to be completely sequenced. We have developed a targeted hybrid-capture method aimed at comprehensive genomic sequencing of wild-type PUUV isolates and the identification of other Orthohantaviruses. Our custom-designed panel includes >11,200 probes covering the entire Orthohantavirus genus. Using this panel, we sequenced complete viral genomes from bank vole lung tissue, human plasma samples, and cell-cultured reference strains. Analysis revealed that Swedish PUUV isolates belong to the Northern Scandinavian lineage, with nucleotide diversity ranging from 2.8 % to 3.7 % among them. Notably, no significant genotypic differences were observed between the viral sequences from reservoirs and human cases except in the nonstructural protein. Despite the high endemicity of PUUV in Northern Sweden, these are the first complete Swedish wild-type PUUV genomes and substantially increase our understanding of PUUV evolution and epidemiology. The panel's sensitivity enables genomic sequencing of human samples with viral RNA levels reflecting the natural progression of infection and underscores our panel's diagnostic value, and could help to uncover novel Orthohantavirus transmission routes.
Language	English
Publishing date	2024-03-30
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1446080-4
ISSN	1873-5967 ; 1386-6532
ISSN (online)	1873-5967
ISSN	1386-6532
DOI	10.1016/j.jcv.2024.105672
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