Table Info

Table 2.

Recommendation of immune-modulating therapeutics according to NIH COVID-19 treatment guidelines as of November 2021 [16] and current status of clinical development according to ClinicalTrials.gov as of December 2021

Target	Drug	Clinical relevance and level of development
NFκB inhibition	¹Corticosteroids (Dexamethasone, prednisone, methylprednisolone, hydrocortisone)	Recommendation: hospitalized patients require supplemental oxygen, high-flow device or non-invasive ventilation, invasive ventilation, ECMO
IL-1Ra	²Anakinra	Clinical trials (phase II/III) Insufficient evidence
IL-1	³Canakinumab	Recommendation against, except clinical trials
JAK 1/2 kinase JAK 1/3 kinase	⁴Baricitinib (Ruxolitinib) alternatively ⁴Tofacitinib	Recommendation: hospitalized patients require high-flow device or non-invasive ventilation (Not in combination with anti-IL6R/anti-IL-6)
GM-CSF	³Gimsilumab ³Mavrilimumab	Clinical trials (phase II) Clinical trials (phase II/III) Insufficient evidence
IL-6	³Toculizumab (anti-IL-6R) alternatively ³Siltuximab (anti-IL-6)	Recommendation: hospitalized patients require high-flow device or non-invasive ventilation, invasive ventilation, ECMO (Not in combination with JAK inhibition)
IL-4, IL-13	³Dupilumab	Clinical trials (phase II)
IL-17	³Ixekizumab	Clinical trials (phase III)
IL-2	⁵Aldesleukin	Clinical trials (phase III)
ICAM-1	-	-
IL-10	-	-
IL-15	⁵N-803	Clinical trials (phase I)
IL-7	⁵CYT107	Clinical trials (phase II)
TNF-α	³Adalimumab ³Infliximab	Clinical trials (phase III) Clinical trials (phase II/III)
Complement C3	⁴APL-9 ⁴AMY-101	Clinical trials (phase I/II) Clinical trials (phase II)
Complement C5	³Ravulizumab ³Zilucoplan	Clinical trials (phase III) Clinical trials (phase II)
Complement C5a	³Avdoralimab (anti-C5a-R) ³Vilobelimab (anti-C5a)	Clinical trials (phase III) Clinical trials (phase II/III)
VCAM1	-	-

Mode of action is classified in: 1

corticoids; 2

antagonists; 3

antibodies; 4

small molecule; 5

agonists. NFκB: nuclear factor kappa B; ECMO: extracorporeal membrane oxygenation; -: no targeting drug, no drug in development, no drug with clinical relevance

Declarations

Acknowledgments

We thank Edith Walther for her tremendous technical support in performing elaborate cell experiments and sample preparation in the initial stages of conceptual work. Tremendous support by Petra and Peter Bauer, Davina Miglietta, Lars Kaiser, the staff at Riesling Apotheke (Ellerstadt, Germany), Europa Apotheke, (Bensheim, Germany), and Apotheke im Markt (Heidelberg, Germany) is gratefully acknowledged.

Author contributions

MB conceived the work; MB, OS, RC, and HPD wrote the manuscript. All authors contributed to manuscript revision, read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Funding from the Institute of Precision Medicine and the Institute for Applied Research (IAF, Furtwangen University, Schwenningen, Germany) is gratefully acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

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