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Early combination therapy of COVID-19 in high-risk patients
Purpose Prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been observed in immunocompromised hosts. Early monotherapy with direct-acting antivirals or monoclonal antibodies, as recommended by the international guidelines, does not prevent this with certainty. Dua...
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| Published in: | Infection 2024-06, Vol.52 (3), p.877-889 |
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| container_end_page | 889 |
| container_issue | 3 |
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| container_title | Infection |
| container_volume | 52 |
| creator | Orth, Hans Martin Flasshove, Charlotte Berger, Moritz Hattenhauer, Tessa Biederbick, Kaja D. Mispelbaum, Rebekka Klein, Uwe Stemler, Jannik Fisahn, Matthis Doleschall, Anna D. Baermann, Ben-Niklas Koenigshausen, Eva Tselikmann, Olga Killer, Alexander de Angelis, Clara Gliga, Smaranda Stegbauer, Johannes Spuck, Nikolai Silling, Gerda Rockstroh, Jürgen K. Strassburg, Christian P. Brossart, Peter Panse, Jens P. Jensen, Björn-Erik Ole Luedde, Tom Boesecke, Christoph Heine, Annkristin Cornely, Oliver A. Monin, Malte B. |
| description | Purpose
Prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been observed in immunocompromised hosts. Early monotherapy with direct-acting antivirals or monoclonal antibodies, as recommended by the international guidelines, does not prevent this with certainty. Dual therapies may therefore have a synergistic effect.
Methods
This retrospective, multicentre study compared treatment strategies for corona virus disease-19 (COVID-19) with combinations of nirmatrelvir/ritonavir, remdesivir, molnupiravir, and/ or mABs during the Omicron surge. Co-primary endpoints were prolonged viral shedding (≥ 10
6
copies/ml at day 21 after treatment initiation) and days with SARS-CoV-2 viral load ≥ 10
6
copies/ml. Therapeutic strategies and risk groups were compared using odds ratios and Fisher’s tests or Kaplan−Meier analysis and long-rank tests. Multivariable regression analysis was performed.
Results
144 patients were included with a median duration of SARS-CoV-2 viral load ≥ 10
6
copies/ml of 8.0 days (IQR 6.0–15.3). Underlying haematological malignancies (HM) (
p
= 0.03) and treatment initiation later than five days after diagnosis (
p
|
| doi_str_mv | 10.1007/s15010-023-02125-5 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11142969</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3062787517</sourcerecordid><originalsourceid>FETCH-LOGICAL-c475t-c592478f1087fba859182e1d75c0677022aebe91428ecf6881855d254fc9b4833</originalsourceid><addsrcrecordid>eNp9kU1vEzEQhq2qiIbAH-ihWqkXLoYZf6xt9YCqUKBSpV6Aq-V1vInbzTrYG6T8ewwpLXDgMJrDPPPOx0vIKcIbBFBvC0pAoMB4DWSSyiMyQ8ENBaP4MZkBB6AaWXtCXpRyBwDSCPWcnHANqLgQM3Jx5fKwb3zadHF0U0xjM61Ddtt9k_pmcfv1-j1F08SxWcfVmuZY7ptt5cI4lZfkWe-GEl495Dn58uHq8-ITvbn9eL24vKFeKDlRLw0TSvcIWvWd09KgZgGXSnpolQLGXOiCQcF08H2rNWopl0yK3ptOaM7n5N1Bd7vrNmHp6-zsBrvNcePy3iYX7d-VMa7tKn23iFXUtKYqvH5QyOnbLpTJbmLxYRjcGNKuWKaNZHVN0BU9_we9S7s81vssh5YprWR93ZywA-VzKiWH_nEbBPvTHHswx1Zz7C9zrKxNZ3_e8djy240K8ANQamlchfw0-z-yPwCCd5ex</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3062787517</pqid></control><display><type>article</type><title>Early combination therapy of COVID-19 in high-risk patients</title><source>Springer Nature</source><creator>Orth, Hans Martin ; Flasshove, Charlotte ; Berger, Moritz ; Hattenhauer, Tessa ; Biederbick, Kaja D. ; Mispelbaum, Rebekka ; Klein, Uwe ; Stemler, Jannik ; Fisahn, Matthis ; Doleschall, Anna D. ; Baermann, Ben-Niklas ; Koenigshausen, Eva ; Tselikmann, Olga ; Killer, Alexander ; de Angelis, Clara ; Gliga, Smaranda ; Stegbauer, Johannes ; Spuck, Nikolai ; Silling, Gerda ; Rockstroh, Jürgen K. ; Strassburg, Christian P. ; Brossart, Peter ; Panse, Jens P. ; Jensen, Björn-Erik Ole ; Luedde, Tom ; Boesecke, Christoph ; Heine, Annkristin ; Cornely, Oliver A. ; Monin, Malte B.</creator><creatorcontrib>Orth, Hans Martin ; Flasshove, Charlotte ; Berger, Moritz ; Hattenhauer, Tessa ; Biederbick, Kaja D. ; Mispelbaum, Rebekka ; Klein, Uwe ; Stemler, Jannik ; Fisahn, Matthis ; Doleschall, Anna D. ; Baermann, Ben-Niklas ; Koenigshausen, Eva ; Tselikmann, Olga ; Killer, Alexander ; de Angelis, Clara ; Gliga, Smaranda ; Stegbauer, Johannes ; Spuck, Nikolai ; Silling, Gerda ; Rockstroh, Jürgen K. ; Strassburg, Christian P. ; Brossart, Peter ; Panse, Jens P. ; Jensen, Björn-Erik Ole ; Luedde, Tom ; Boesecke, Christoph ; Heine, Annkristin ; Cornely, Oliver A. ; Monin, Malte B.</creatorcontrib><description>Purpose
Prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been observed in immunocompromised hosts. Early monotherapy with direct-acting antivirals or monoclonal antibodies, as recommended by the international guidelines, does not prevent this with certainty. Dual therapies may therefore have a synergistic effect.
Methods
This retrospective, multicentre study compared treatment strategies for corona virus disease-19 (COVID-19) with combinations of nirmatrelvir/ritonavir, remdesivir, molnupiravir, and/ or mABs during the Omicron surge. Co-primary endpoints were prolonged viral shedding (≥ 10
6
copies/ml at day 21 after treatment initiation) and days with SARS-CoV-2 viral load ≥ 10
6
copies/ml. Therapeutic strategies and risk groups were compared using odds ratios and Fisher’s tests or Kaplan−Meier analysis and long-rank tests. Multivariable regression analysis was performed.
Results
144 patients were included with a median duration of SARS-CoV-2 viral load ≥ 10
6
copies/ml of 8.0 days (IQR 6.0–15.3). Underlying haematological malignancies (HM) (
p
= 0.03) and treatment initiation later than five days after diagnosis (
p
< 0.01) were significantly associated with longer viral shedding. Prolonged viral shedding was observed in 14.6% (
n
= 21/144), particularly in patients with underlying HM (OR 3.5; 95% CI 1.2–9.9;
p
= 0.02). Clinical courses of COVID-19 were mild to moderate with only few adverse effects potentially related to combination treatment.
Conclusion
Early combination treatment of COVID-19 effectively prevented prolonged viral shedding in 85.6% of cases. Considering the rapid viral clearance rates and low toxicity, individualized dual therapy approaches may be beneficial in high-risk patients.</description><identifier>ISSN: 0300-8126</identifier><identifier>ISSN: 1439-0973</identifier><identifier>EISSN: 1439-0973</identifier><identifier>DOI: 10.1007/s15010-023-02125-5</identifier><identifier>PMID: 38017344</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adenosine Monophosphate - analogs & derivatives ; Adenosine Monophosphate - therapeutic use ; Adult ; Aged ; Alanine - analogs & derivatives ; Alanine - therapeutic use ; Antibodies, Monoclonal - therapeutic use ; Antiviral agents ; Antiviral Agents - therapeutic use ; Coronaviruses ; COVID-19 ; COVID-19 - virology ; COVID-19 Drug Treatment ; Cytidine - analogs & derivatives ; Drug Therapy, Combination ; Family Medicine ; Female ; General Practice ; Health services ; Humans ; Hydroxylamines ; Immunocompromised hosts ; Infectious Diseases ; Internal Medicine ; Male ; Malignancy ; Medicine ; Medicine & Public Health ; Middle Aged ; Monoclonal antibodies ; Patients ; Rank tests ; Regression analysis ; Retrospective Studies ; Risk ; Risk groups ; Ritonavir ; Ritonavir - therapeutic use ; SARS-CoV-2 - drug effects ; Severe acute respiratory syndrome coronavirus 2 ; Synergistic effect ; Toxicity ; Viral diseases ; Viral Load - drug effects ; Virus Shedding - drug effects</subject><ispartof>Infection, 2024-06, Vol.52 (3), p.877-889</ispartof><rights>The Author(s) 2023</rights><rights>2023. The Author(s).</rights><rights>Copyright Springer Nature B.V. Jun 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-c592478f1087fba859182e1d75c0677022aebe91428ecf6881855d254fc9b4833</citedby><cites>FETCH-LOGICAL-c475t-c592478f1087fba859182e1d75c0677022aebe91428ecf6881855d254fc9b4833</cites><orcidid>0000-0002-8794-3612</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38017344$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Orth, Hans Martin</creatorcontrib><creatorcontrib>Flasshove, Charlotte</creatorcontrib><creatorcontrib>Berger, Moritz</creatorcontrib><creatorcontrib>Hattenhauer, Tessa</creatorcontrib><creatorcontrib>Biederbick, Kaja D.</creatorcontrib><creatorcontrib>Mispelbaum, Rebekka</creatorcontrib><creatorcontrib>Klein, Uwe</creatorcontrib><creatorcontrib>Stemler, Jannik</creatorcontrib><creatorcontrib>Fisahn, Matthis</creatorcontrib><creatorcontrib>Doleschall, Anna D.</creatorcontrib><creatorcontrib>Baermann, Ben-Niklas</creatorcontrib><creatorcontrib>Koenigshausen, Eva</creatorcontrib><creatorcontrib>Tselikmann, Olga</creatorcontrib><creatorcontrib>Killer, Alexander</creatorcontrib><creatorcontrib>de Angelis, Clara</creatorcontrib><creatorcontrib>Gliga, Smaranda</creatorcontrib><creatorcontrib>Stegbauer, Johannes</creatorcontrib><creatorcontrib>Spuck, Nikolai</creatorcontrib><creatorcontrib>Silling, Gerda</creatorcontrib><creatorcontrib>Rockstroh, Jürgen K.</creatorcontrib><creatorcontrib>Strassburg, Christian P.</creatorcontrib><creatorcontrib>Brossart, Peter</creatorcontrib><creatorcontrib>Panse, Jens P.</creatorcontrib><creatorcontrib>Jensen, Björn-Erik Ole</creatorcontrib><creatorcontrib>Luedde, Tom</creatorcontrib><creatorcontrib>Boesecke, Christoph</creatorcontrib><creatorcontrib>Heine, Annkristin</creatorcontrib><creatorcontrib>Cornely, Oliver A.</creatorcontrib><creatorcontrib>Monin, Malte B.</creatorcontrib><title>Early combination therapy of COVID-19 in high-risk patients</title><title>Infection</title><addtitle>Infection</addtitle><addtitle>Infection</addtitle><description>Purpose
Prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been observed in immunocompromised hosts. Early monotherapy with direct-acting antivirals or monoclonal antibodies, as recommended by the international guidelines, does not prevent this with certainty. Dual therapies may therefore have a synergistic effect.
Methods
This retrospective, multicentre study compared treatment strategies for corona virus disease-19 (COVID-19) with combinations of nirmatrelvir/ritonavir, remdesivir, molnupiravir, and/ or mABs during the Omicron surge. Co-primary endpoints were prolonged viral shedding (≥ 10
6
copies/ml at day 21 after treatment initiation) and days with SARS-CoV-2 viral load ≥ 10
6
copies/ml. Therapeutic strategies and risk groups were compared using odds ratios and Fisher’s tests or Kaplan−Meier analysis and long-rank tests. Multivariable regression analysis was performed.
Results
144 patients were included with a median duration of SARS-CoV-2 viral load ≥ 10
6
copies/ml of 8.0 days (IQR 6.0–15.3). Underlying haematological malignancies (HM) (
p
= 0.03) and treatment initiation later than five days after diagnosis (
p
< 0.01) were significantly associated with longer viral shedding. Prolonged viral shedding was observed in 14.6% (
n
= 21/144), particularly in patients with underlying HM (OR 3.5; 95% CI 1.2–9.9;
p
= 0.02). Clinical courses of COVID-19 were mild to moderate with only few adverse effects potentially related to combination treatment.
Conclusion
Early combination treatment of COVID-19 effectively prevented prolonged viral shedding in 85.6% of cases. Considering the rapid viral clearance rates and low toxicity, individualized dual therapy approaches may be beneficial in high-risk patients.</description><subject>Adenosine Monophosphate - analogs & derivatives</subject><subject>Adenosine Monophosphate - therapeutic use</subject><subject>Adult</subject><subject>Aged</subject><subject>Alanine - analogs & derivatives</subject><subject>Alanine - therapeutic use</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antiviral agents</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>COVID-19 - virology</subject><subject>COVID-19 Drug Treatment</subject><subject>Cytidine - analogs & derivatives</subject><subject>Drug Therapy, Combination</subject><subject>Family Medicine</subject><subject>Female</subject><subject>General Practice</subject><subject>Health services</subject><subject>Humans</subject><subject>Hydroxylamines</subject><subject>Immunocompromised hosts</subject><subject>Infectious Diseases</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Malignancy</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Monoclonal antibodies</subject><subject>Patients</subject><subject>Rank tests</subject><subject>Regression analysis</subject><subject>Retrospective Studies</subject><subject>Risk</subject><subject>Risk groups</subject><subject>Ritonavir</subject><subject>Ritonavir - therapeutic use</subject><subject>SARS-CoV-2 - drug effects</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Synergistic effect</subject><subject>Toxicity</subject><subject>Viral diseases</subject><subject>Viral Load - drug effects</subject><subject>Virus Shedding - drug effects</subject><issn>0300-8126</issn><issn>1439-0973</issn><issn>1439-0973</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kU1vEzEQhq2qiIbAH-ihWqkXLoYZf6xt9YCqUKBSpV6Aq-V1vInbzTrYG6T8ewwpLXDgMJrDPPPOx0vIKcIbBFBvC0pAoMB4DWSSyiMyQ8ENBaP4MZkBB6AaWXtCXpRyBwDSCPWcnHANqLgQM3Jx5fKwb3zadHF0U0xjM61Ddtt9k_pmcfv1-j1F08SxWcfVmuZY7ptt5cI4lZfkWe-GEl495Dn58uHq8-ITvbn9eL24vKFeKDlRLw0TSvcIWvWd09KgZgGXSnpolQLGXOiCQcF08H2rNWopl0yK3ptOaM7n5N1Bd7vrNmHp6-zsBrvNcePy3iYX7d-VMa7tKn23iFXUtKYqvH5QyOnbLpTJbmLxYRjcGNKuWKaNZHVN0BU9_we9S7s81vssh5YprWR93ZywA-VzKiWH_nEbBPvTHHswx1Zz7C9zrKxNZ3_e8djy240K8ANQamlchfw0-z-yPwCCd5ex</recordid><startdate>20240601</startdate><enddate>20240601</enddate><creator>Orth, Hans Martin</creator><creator>Flasshove, Charlotte</creator><creator>Berger, Moritz</creator><creator>Hattenhauer, Tessa</creator><creator>Biederbick, Kaja D.</creator><creator>Mispelbaum, Rebekka</creator><creator>Klein, Uwe</creator><creator>Stemler, Jannik</creator><creator>Fisahn, Matthis</creator><creator>Doleschall, Anna D.</creator><creator>Baermann, Ben-Niklas</creator><creator>Koenigshausen, Eva</creator><creator>Tselikmann, Olga</creator><creator>Killer, Alexander</creator><creator>de Angelis, Clara</creator><creator>Gliga, Smaranda</creator><creator>Stegbauer, Johannes</creator><creator>Spuck, Nikolai</creator><creator>Silling, Gerda</creator><creator>Rockstroh, Jürgen K.</creator><creator>Strassburg, Christian P.</creator><creator>Brossart, Peter</creator><creator>Panse, Jens P.</creator><creator>Jensen, Björn-Erik Ole</creator><creator>Luedde, Tom</creator><creator>Boesecke, Christoph</creator><creator>Heine, Annkristin</creator><creator>Cornely, Oliver A.</creator><creator>Monin, Malte B.</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8794-3612</orcidid></search><sort><creationdate>20240601</creationdate><title>Early combination therapy of COVID-19 in high-risk patients</title><author>Orth, Hans Martin ; Flasshove, Charlotte ; Berger, Moritz ; Hattenhauer, Tessa ; Biederbick, Kaja D. ; Mispelbaum, Rebekka ; Klein, Uwe ; Stemler, Jannik ; Fisahn, Matthis ; Doleschall, Anna D. ; Baermann, Ben-Niklas ; Koenigshausen, Eva ; Tselikmann, Olga ; Killer, Alexander ; de Angelis, Clara ; Gliga, Smaranda ; Stegbauer, Johannes ; Spuck, Nikolai ; Silling, Gerda ; Rockstroh, Jürgen K. ; Strassburg, Christian P. ; Brossart, Peter ; Panse, Jens P. ; Jensen, Björn-Erik Ole ; Luedde, Tom ; Boesecke, Christoph ; Heine, Annkristin ; Cornely, Oliver A. ; Monin, Malte B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-c592478f1087fba859182e1d75c0677022aebe91428ecf6881855d254fc9b4833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adenosine Monophosphate - analogs & derivatives</topic><topic>Adenosine Monophosphate - therapeutic use</topic><topic>Adult</topic><topic>Aged</topic><topic>Alanine - analogs & derivatives</topic><topic>Alanine - therapeutic use</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Antiviral agents</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Coronaviruses</topic><topic>COVID-19</topic><topic>COVID-19 - virology</topic><topic>COVID-19 Drug Treatment</topic><topic>Cytidine - analogs & derivatives</topic><topic>Drug Therapy, Combination</topic><topic>Family Medicine</topic><topic>Female</topic><topic>General Practice</topic><topic>Health services</topic><topic>Humans</topic><topic>Hydroxylamines</topic><topic>Immunocompromised hosts</topic><topic>Infectious Diseases</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Malignancy</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Monoclonal antibodies</topic><topic>Patients</topic><topic>Rank tests</topic><topic>Regression analysis</topic><topic>Retrospective Studies</topic><topic>Risk</topic><topic>Risk groups</topic><topic>Ritonavir</topic><topic>Ritonavir - therapeutic use</topic><topic>SARS-CoV-2 - drug effects</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Synergistic effect</topic><topic>Toxicity</topic><topic>Viral diseases</topic><topic>Viral Load - drug effects</topic><topic>Virus Shedding - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Orth, Hans Martin</creatorcontrib><creatorcontrib>Flasshove, Charlotte</creatorcontrib><creatorcontrib>Berger, Moritz</creatorcontrib><creatorcontrib>Hattenhauer, Tessa</creatorcontrib><creatorcontrib>Biederbick, Kaja D.</creatorcontrib><creatorcontrib>Mispelbaum, Rebekka</creatorcontrib><creatorcontrib>Klein, Uwe</creatorcontrib><creatorcontrib>Stemler, Jannik</creatorcontrib><creatorcontrib>Fisahn, Matthis</creatorcontrib><creatorcontrib>Doleschall, Anna D.</creatorcontrib><creatorcontrib>Baermann, Ben-Niklas</creatorcontrib><creatorcontrib>Koenigshausen, Eva</creatorcontrib><creatorcontrib>Tselikmann, Olga</creatorcontrib><creatorcontrib>Killer, Alexander</creatorcontrib><creatorcontrib>de Angelis, Clara</creatorcontrib><creatorcontrib>Gliga, Smaranda</creatorcontrib><creatorcontrib>Stegbauer, Johannes</creatorcontrib><creatorcontrib>Spuck, Nikolai</creatorcontrib><creatorcontrib>Silling, Gerda</creatorcontrib><creatorcontrib>Rockstroh, Jürgen K.</creatorcontrib><creatorcontrib>Strassburg, Christian P.</creatorcontrib><creatorcontrib>Brossart, Peter</creatorcontrib><creatorcontrib>Panse, Jens P.</creatorcontrib><creatorcontrib>Jensen, Björn-Erik Ole</creatorcontrib><creatorcontrib>Luedde, Tom</creatorcontrib><creatorcontrib>Boesecke, Christoph</creatorcontrib><creatorcontrib>Heine, Annkristin</creatorcontrib><creatorcontrib>Cornely, Oliver A.</creatorcontrib><creatorcontrib>Monin, Malte B.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Infection</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Orth, Hans Martin</au><au>Flasshove, Charlotte</au><au>Berger, Moritz</au><au>Hattenhauer, Tessa</au><au>Biederbick, Kaja D.</au><au>Mispelbaum, Rebekka</au><au>Klein, Uwe</au><au>Stemler, Jannik</au><au>Fisahn, Matthis</au><au>Doleschall, Anna D.</au><au>Baermann, Ben-Niklas</au><au>Koenigshausen, Eva</au><au>Tselikmann, Olga</au><au>Killer, Alexander</au><au>de Angelis, Clara</au><au>Gliga, Smaranda</au><au>Stegbauer, Johannes</au><au>Spuck, Nikolai</au><au>Silling, Gerda</au><au>Rockstroh, Jürgen K.</au><au>Strassburg, Christian P.</au><au>Brossart, Peter</au><au>Panse, Jens P.</au><au>Jensen, Björn-Erik Ole</au><au>Luedde, Tom</au><au>Boesecke, Christoph</au><au>Heine, Annkristin</au><au>Cornely, Oliver A.</au><au>Monin, Malte B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Early combination therapy of COVID-19 in high-risk patients</atitle><jtitle>Infection</jtitle><stitle>Infection</stitle><addtitle>Infection</addtitle><date>2024-06-01</date><risdate>2024</risdate><volume>52</volume><issue>3</issue><spage>877</spage><epage>889</epage><pages>877-889</pages><issn>0300-8126</issn><issn>1439-0973</issn><eissn>1439-0973</eissn><abstract>Purpose
Prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been observed in immunocompromised hosts. Early monotherapy with direct-acting antivirals or monoclonal antibodies, as recommended by the international guidelines, does not prevent this with certainty. Dual therapies may therefore have a synergistic effect.
Methods
This retrospective, multicentre study compared treatment strategies for corona virus disease-19 (COVID-19) with combinations of nirmatrelvir/ritonavir, remdesivir, molnupiravir, and/ or mABs during the Omicron surge. Co-primary endpoints were prolonged viral shedding (≥ 10
6
copies/ml at day 21 after treatment initiation) and days with SARS-CoV-2 viral load ≥ 10
6
copies/ml. Therapeutic strategies and risk groups were compared using odds ratios and Fisher’s tests or Kaplan−Meier analysis and long-rank tests. Multivariable regression analysis was performed.
Results
144 patients were included with a median duration of SARS-CoV-2 viral load ≥ 10
6
copies/ml of 8.0 days (IQR 6.0–15.3). Underlying haematological malignancies (HM) (
p
= 0.03) and treatment initiation later than five days after diagnosis (
p
< 0.01) were significantly associated with longer viral shedding. Prolonged viral shedding was observed in 14.6% (
n
= 21/144), particularly in patients with underlying HM (OR 3.5; 95% CI 1.2–9.9;
p
= 0.02). Clinical courses of COVID-19 were mild to moderate with only few adverse effects potentially related to combination treatment.
Conclusion
Early combination treatment of COVID-19 effectively prevented prolonged viral shedding in 85.6% of cases. Considering the rapid viral clearance rates and low toxicity, individualized dual therapy approaches may be beneficial in high-risk patients.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>38017344</pmid><doi>10.1007/s15010-023-02125-5</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-8794-3612</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0300-8126 |
| ispartof | Infection, 2024-06, Vol.52 (3), p.877-889 |
| issn | 0300-8126 1439-0973 1439-0973 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11142969 |
| source | Springer Nature |
| subjects | Adenosine Monophosphate - analogs & derivatives Adenosine Monophosphate - therapeutic use Adult Aged Alanine - analogs & derivatives Alanine - therapeutic use Antibodies, Monoclonal - therapeutic use Antiviral agents Antiviral Agents - therapeutic use Coronaviruses COVID-19 COVID-19 - virology COVID-19 Drug Treatment Cytidine - analogs & derivatives Drug Therapy, Combination Family Medicine Female General Practice Health services Humans Hydroxylamines Immunocompromised hosts Infectious Diseases Internal Medicine Male Malignancy Medicine Medicine & Public Health Middle Aged Monoclonal antibodies Patients Rank tests Regression analysis Retrospective Studies Risk Risk groups Ritonavir Ritonavir - therapeutic use SARS-CoV-2 - drug effects Severe acute respiratory syndrome coronavirus 2 Synergistic effect Toxicity Viral diseases Viral Load - drug effects Virus Shedding - drug effects |
| title | Early combination therapy of COVID-19 in high-risk patients |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-20T16%3A43%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Early%20combination%20therapy%20of%20COVID-19%20in%20high-risk%20patients&rft.jtitle=Infection&rft.au=Orth,%20Hans%20Martin&rft.date=2024-06-01&rft.volume=52&rft.issue=3&rft.spage=877&rft.epage=889&rft.pages=877-889&rft.issn=0300-8126&rft.eissn=1439-0973&rft_id=info:doi/10.1007/s15010-023-02125-5&rft_dat=%3Cproquest_pubme%3E3062787517%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c475t-c592478f1087fba859182e1d75c0677022aebe91428ecf6881855d254fc9b4833%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=3062787517&rft_id=info:pmid/38017344&rfr_iscdi=true |