\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[T2A]{fontenc}
\usepackage[polish,ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Corticosteroids and COVID-19 vaccine: a challenging issue}



\author[1]{Shervin Shokouhi}%
\author[1]{Atousa  Hakamifard}%
\affil[1]{Shahid Beheshti University of Medical Sciences}%


\vspace{-1em}



  
  \date{June 04, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup








\sloppy


\textbf{Corticosteroids and COVID-19 vaccine: a challenging issue}

\emph{To the editor;}

In the pandemic era of COVID-19 vaccines, patients on immunosuppressive
medications need special considerations. Immunosuppression can disturb
the effectiveness of the vaccine responses. Thus establishing a proper
recommendation for vaccination in these patients would be challenging.
The immunosuppressive effects of corticosteroids (CS) vary and depend on
its duration of use and doses. Doses more than 40 mg/ day prednisone for
more than one week or [?] 20 mg of prednisone or equivalent for [?] two
weeks, induce immunosuppression (1, 2). Till now the current
recommendations for COVID-19 vaccines and CS administration are mostly
based on the available evidence for killed vaccines (e.g., influenza).

Choosing the best time to increase the efficacy of vaccination is
important in immunosuppressed patients. Also each country's vaccine
policy is important to set out vaccination times in these specific
groups. In some countries, especially developing countries, the COVID-19
vaccination schedule is not adjustable by the patients or physicians,
and selecting a particular time window for the best efficacy of
immunization is impossible. However, if the vaccination schedule is not
adaptable, vaccination is recommended with any vaccine when available.
If the schedules are adjustable, the following issues are considered:

Evidences showed that with the dose of up to 20 mg/day prednisone or
equivalents, the response to inactivated vaccines could not be
suppressed, and these patients can receive vaccine safely. Patients
treated with prednisone at a dose of less than 20 mg/day are not
immunocompromised and have sufficient immune response (1, 2).

The immunosuppressive doses of CS are [?] 20 mg/day for [?] 2 weeks, or
\textgreater{} 40 mg prednisone for \textgreater{} 1 week. The ideal
time for vaccination in this group is one month after discontinuation of
the CS treatment to elicit an adequate immune response (1). If it was
not possible to end the CS treatment, a vaccine should be given when
receiving the lowest dose of CS. For example, the dose of CS can be
reduced to less than 20 mg with or without the addition of steroids
sparing drugs (e.g., azathioprine) , and then at least two weeks after
vaccination, the dose of the drug returns to the previous state (3).

Suppose the patient is a candidate for CS therapy with doses of [?] 20 mg
prednisone for [?] two weeks or \textgreater{} 40 mg prednisone for
\textgreater{} 1 week. In this case, it is suggested that vaccine be
administered at least 2 weeks before immunosuppression initiation
because two weeks are required to develop an immune response (2). But if
the CS administration cannot be withheld after vaccination because of
disease flare or if the patient may not have access to the vaccine with
the recommended interval, we recommend ordering the vaccine considering
a suboptimal response to the vaccine.

Corticosteroid pulse therapy does not cause immunodeficiency, and the
vaccine should not be delayed (4).

If a country's vaccination policy is such that the clinicians can choose
the type of vaccine, it is better to choose a vaccine based on the
underlying disease and the number of days that they can reduce the
steroid dose. If the patient's corticosteroid dose cannot be reduced for
an extended time and there is a risk of disease flare, it is better to
use vaccines with less interval time between two doses.

The immunogenicity of a single dose of some vaccines is likely to be
acceptable in patients who have natural antibodies and are infected
before. In the future, only one dose of the vaccine may be sufficient in
these patients (5, 6). Therefore, it is better to adjust vaccination in
this group of patients to gain the most effect from one of the two
doses. It is better to focus on boosting the impact of at least one of
the vaccine doses.

For patients under CS therapy who are immunocompromised, we suggest
using a highly effective vaccine. The best vaccines with the best
efficacy in this group of patients are not determined. These vaccines
may be with mRNA or vector-based systems. Further clinical trial studies
are required. These considerations can be used as long as more data are
available.

\textbf{Funding:} None.

\textbf{Competing Interests:} None declared.

\textbf{Ethical Approval:} Not required.

\textbf{References:}

\begin{enumerate}
\tightlist
\item
  Immunisation of immunocompromised patients.
  https://www.hse.ie/eng/health/immunisation/hcpinfo/guidelines/chapter3.pdf.
\item
  Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M,
  Bousvaros A, Dhanireddy S, Sung L, Keyserling H, Kang I. 2013 IDSA
  clinical practice guideline for vaccination of the immunocompromised
  host. Clinical infectious diseases. 2014 Feb 1; 58(3):e44-100.
\item
  Tanr\selectlanguage{polish}ı\selectlanguage{ngerman}över MD, Akar S, Türkçapar N, Karada\selectlanguage{polish}ğ \selectlanguage{ngerman}Ö, Ertenli \selectlanguage{polish}İ, \selectlanguage{english}Kiraz S.
  Vaccination recommendations for adult patients with rheumatic
  diseases. European journal of rheumatology. 2016 Mar; 3(1):29.
\item
  Fan PT, Yu DT, Clements PJ, Fowlston S, Eisman J, and Bluestone R.
  Effect of corticosteroids on the human immune response: comparison of
  one and three daily 1 gm intravenous pulses of methylprednisolone. J
  Lab Clin Med. 1978 Apr; 91(4):625-34.
\item
  Samanovic MI, Cornelius AR, Wilson JP, Karmacharya T, Gray-Gaillard
  SL, Allen JR, Hyman SW, Moritz G, Ali M, Koralov SB, Mulligan MJ. Poor
  antigen-specific responses to the second BNT162b2 mRNA vaccine dose in
  SARS-CoV-2-experienced individuals. medRxiv. 2021 Jan 1.
\item
  Chahla RE, Tomas-Grau RH, Cazorla SI, Ploper D, Pingitore EV, Lopez
  MA, Aznar P, Alcorta ME, del Mar Velez EM, Stagnetto A, Avila CL. Past
  SARS-CoV-2 infection elicits a strong immune response after a single
  vaccine dose. medRxiv. 2021 Jan 1.
\end{enumerate}

\selectlanguage{english}
\FloatBarrier
\end{document}

