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\begin{document}

\title{COVID-19 IN PATIENTS RECOVERING FROM CARDIAC SURGERY: A SURPRISING MILD
DISEASE COURSE}



\author[1]{Alfredo Cerillo}%
\author[2]{Niccolò Marchionni}%
\author[1]{Beatrice Bacchi}%
\author[3]{Pier Luigi Stefano}%
\affil[1]{Azienda Ospedaliero Universitaria Careggi}%
\affil[2]{Azienda Ospedaliero-Universitaria Careggi}%
\affil[3]{University Hospital Careggi}%


\vspace{-1em}



  
  \date{May 27, 2024}


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\selectlanguage{english}
\begin{abstract}
Cardiac surgical patients are often discharged to a rehabilitation
facility to complete the convalescence in a protected setting. This care
pathway is usually reserved for elderly and fragile patients, with
severe and invalidating comorbid conditions. Between March and April
2020, nineteen patients were discharged from our unit to a
rehabilitation clinic where a hotbed of SARS-CoV-2 infection was
documented on April 17. After the outbreak, all patients underwent
screening with real-time PCR on nasal swabs, and 18/19 patients were
found positive. Diversely from other observations on perioperative
COVID-19 reporting mortality rates of 30-40\%, the COVID-19 had a benign
course in our cohort: six patients were completely asymptomatic, and
only seven patients required hospitalization (no deaths). We describe
the baseline, operative and postoperative features of these patients,
and present some potential explanations for the surprisingly benign
course of the COVID-19 in this cohort.%
\end{abstract}%



\sloppy


COVID-19 IN PATIENTS RECOVERING FROM CARDIAC SURGERY: A SURPRISING MILD
DISEASE COURSE

Alfredo Giuseppe Cerillo, MD\textsuperscript{1}, Niccol\selectlanguage{ngerman}ò Marchionni, MD,
PhD\textsuperscript{2,3}, Beatrice Bacchi, MD\textsuperscript{3},
Pierluigi Stefàno, MD, PhD\textsuperscript{1,3}.

Unit of Cardiac Surgery (1) and Cardiology (2), Careggi University
Hospital; University of Florence School of Medicine (3), Florence,
Italy.

Word count: 1500

Conflict of interest: none

Funding: none

Data available upon request

Corresponding Author: Dr Cerillo, SOD Cardiochirurgia, AOU Careggi,
Largo Brambilla 3, 50141 Firenze, Italy. Email:\emph{acerillo@yahoo.com}

Abstract

Cardiac surgical patients are often discharged to a rehabilitation
facility to complete the convalescence in a protected setting. This care
pathway is usually reserved for elderly and fragile patients, with
severe and invalidating comorbid conditions. Between March and April
2020, nineteen patients were discharged from our unit to a
rehabilitation clinic where a hotbed of SARS-CoV-2 infection was
documented on April 17. After the outbreak, all patients underwent
screening with real-time PCR on nasal swabs, and 18/19 patients were
found positive. Diversely from other observations on perioperative
COVID-19 reporting mortality rates of 30-40\%, the COVID-19 had a benign
course in our cohort: six patients were completely asymptomatic, and
only seven patients required hospitalization (no deaths). We describe
the baseline, operative and postoperative features of these patients,
and present some potential explanations for the surprisingly benign
course of the COVID-19 in this cohort.

Cardiac surgical patients are often discharged to a rehabilitation
facility, to complete the convalescence in a protected setting. This
care pathway is usually reserved for elderly and fragile patients, or
for those with severe comorbid conditions. Between March 23 and April
14, nineteen patients were discharged from our unit to a rehabilitation
clinic where a hotbed of SARS-CoV-2 infection was documented on April
17\textsuperscript{th}. After the outbreak all patients underwent
screening, and 18 were found positive. Here we describe this patient
population. The Internal Review Board approved this study. Oral informed
consent was asked to all patients.

A mild COVID-19 in a high-risk population

The patients' data are reported in Table 1. This was a group of
critically ill patients with severe comorbidities and high risk scores.
The indications to surgery were: aortic dissection (3), congestive heart
failure (13) and endocarditis (2). Five patients had complications (low
output syndrome 3, bleeding 2, renal failure 2, prolonged ventilation
3).

The median interval between the operation and the discharge was 8 days
(range 5 -- 31). Before discharge, all patients underwent screening to
exclude a subclinical SARS-CoV2 infection: all these exams were
negative.

After a median period of 9 days in the rehabilitation clinic (range:
4-24), 18/19 patients presented a SARS-COV2 positive swab. Surprisingly,
the infection had a benign course in this cohort: six patients were
completely asymptomatic, and the remaining had only mild symptoms. Only
six patients had fever and one complained of dyspnea. Seven patients
were hospitalized, and only one needed a short admission in the COVID-19
ICU for dyspnea and mild hypoxemia, that was treated by CPAP. The
remaining eleven patients were discharged home, or to a COVID-19 hotel.
At the latest follow-up (October 31\textsuperscript{st}), all patients
had been discharged home.

Comment

The SARS-COV2 infection can be pauci-symptomatic, causing a flu-like
disease. In some patients, however, it causes severe interstitial
pneumonia and ARDS (1). In a meta-analysis of 34 studies, totaling 6263
patients, the incidence of severe disease and ICU admission ranged
between 9.6\% and 56.3\% (2). Recently, there has been a consistent
effort to identify the risk factors and the mechanisms leading to the
development of severe disease, and there is evidence that comorbid
chronic diseases and acute organ injury might predispose to the
development of ARDS. Older age, obesity, arterial hypertension, COPD and
cardiovascular diseases have been repeatedly indicated as major risk
factors for the development of severe symptoms and death: all these
conditions were highly prevalent in our cohort.

The COVIDSurg Collaborative reported 30-day mortality and pulmonary
complications in 1128 patients with perioperative SARS-CoV-2 infection.
Pulmonary complications were frequent, and associated with an increased
mortality. In the subgroup of 51 cardiac surgical patients, the
incidence of pulmonary complications was as high as 94.1\%, and the
mortality was 34\% (3). Yates and coworkers reported similar results:
all their patients had pulmonary complications, the postoperative
hospital stay was prolonged, and the mortality was 44.4\% (4).
Considering all these data, the benign course of the COVID-19 in our
patients might appear paradoxical.

Chance or causality?

A first, possible explanation of this paradox is stochastic: given that
the true prevalence and mortality rate of the SARS-COV2 infection are
not known, it is possible that the low rate of symptoms and
complications was simply due to chance. Indeed, all patients - not only
those with a clinical suspect of COVID-19 - were tested in the
rehabilitation clinic, and this could have maximized the sensitivity of
the screening program. However, the prevalence of severe comorbid
chronic diseases and risk factors was extremely high in our cohort,
increasing the theoretic risk of a severe covid-19. In fact, data from
other series of perioperative COVID-19 in cardiac surgery showed
ubiquitous pulmonary complications and very high mortality rates (3, 4).

An attractive hypothesis is that our patients were somehow ``protected''
from the COVID-19. All our patients received low molecular weight
heparin during the perioperative period, and all except one were
discharged on oral anticoagulants. An altered hemostasis plays a major
role in the development of severe COVID-19, and anticoagulants might
have exerted a protective effect (5).

Severe COVID-19 is characterized by the development of ARDS, which
eventually leads to ICU admission and death (6). A maladaptive immune
response, involving activation of the innate immunity has been indicated
as the pathogenetic mechanism of ARDS. Cardiac surgery promotes a strong
systemic inflammatory response (7). It is possible that the recent
activation of the innate immunity related to the surgical stress caused
a secondary immunodeficiency in our patients, resulting in a blunted
immune response to the SARS-COV2 infection.

While the potential protective role of a blunted immune response and/or
of the anticoagulant therapy may only be speculated, our population
offers an interesting view on a delicate aspect of the COVID-19
pandemic, that is the occurrence of a cluster of infections in a group
of high-risk hospitalized patients. Eighteen out of 19 patients were
infected, highlighting the contagiousness of the disease. The timing of
the infection is also of interest. All our patients came in contact with
the SARS-CoV2 postoperatively, after 10.0±4.8 days, while previous
series included cases of preoperative infection and/or early
postoperative infection: this could explain the severity of the
perioperative COVID-19 observed by others.

Our data show that the SARS-CoV2 infection after cardiac surgery may
have a benign course. We believe the favorable outcome observed in our
patients along with the negative experiences previously reported
highlight the importance of an aggressive screening to rule out a
preoperative infection (and to postpone the operation in positive
patients whenever possible), and suggest that anticoagulation could help
to prevent the development of severe COVID-19 in these patients. Further
studies are needed to investigate the relationship between the
surgery-induced inflammatory response, anticoagulation and severity of
COVID-19.

REFERENCES

Giusti B, Gori AM, Alessi M, et al. Sars-CoV-2 Induced Coagulopathy and
Prognosis in Hospitalized Patients: A Snapshot From Italy. Thromb
Haemost. 2020.

Wang X, Fang X, Cai Z, et al. Comorbid Chronic Diseases and Acute Organ
Injuries Are Strongly Correlated with Disease Severity and Mortality
among COVID-19 Patients: A Systemic Review and Meta-Analysis.~Research
(Wash D C) 2020:2402961.

COVIDSurg Collaborative. Mortality and pulmonary complications in
patients undergoing surgery with perioperative SARS-CoV-2 infection: an
international cohort study.~Lancet. 2020;S0140-6736(20)31182-X.

Yates MT, Balmforth D, Lopez-Marco A, Uppal R, Oo AY. Outcomes of
patients diagnosed with COVID-19 in the early postoperative period
following cardiac surgery. Interact CardioVasc Thorac Surg 2020;
doi:10.1093/icvts/ivaa143.

Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is
associated with decreased mortality in severe coronavirus disease 2019
patients with coagulopathy.~J Thromb Haemost. 2020;18(5):1094-1099.

Guan WJ, Ni ZY, Hu Y, et al. Clinical Characteristics of Coronavirus
Disease 2019 in China.~N Engl J Med. 2020;382(18):1708-1720.

Giacinto O, Satriano U, Nenna A, et al. Inflammatory Response and
Endothelial Dysfunction Following Cardiopulmonary Bypass:
Pathophysiology and Pharmacological Targets.~Recent Pat Inflamm Allergy
Drug Discov. 2019;13(2):158\selectlanguage{english}-173.

\textbf{Table 1. patients characteristics}\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
\textbf{Demographics and risk factors} & \textbf{Demographics and risk
factors}\tabularnewline
Age (y) & 70.1\selectlanguage{ngerman}±11.9\tabularnewline
Sex, M & 12\tabularnewline
Hypertension & 11\tabularnewline
Diabetes & 2\tabularnewline
Smoking & 7\tabularnewline
Obesity & 4\tabularnewline
drug abuse & 2\tabularnewline
COPD & 6\tabularnewline
Renal failure & 3\tabularnewline
CAD & 4\tabularnewline
lvd & 4\tabularnewline
Pulmonary hypertension & 11\tabularnewline
Preoperative inotropes/IABP & 3\tabularnewline
other chronic condition & 4\tabularnewline
\textbf{Surgical details} & \textbf{Surgical details}\tabularnewline
sts score &\tabularnewline
Emergency & 5\tabularnewline
REDO & 4\tabularnewline
complex combined procedures & 12\tabularnewline
endocarditis & 2\tabularnewline
Aortic dissection & 2\tabularnewline
Major complications & 4\tabularnewline
\textbf{covid-19 related syptoms and course} &\tabularnewline
time to diagnosis & 10.0 \selectlanguage{ngerman}± 4.8\tabularnewline
asymptomatic & 6\tabularnewline
fever & 7\tabularnewline
cough & 3\tabularnewline
sore throat & 2\tabularnewline
dyspnoea & 1\tabularnewline
gi symptoms & 5\tabularnewline
Major rise in PCR levels & 5\tabularnewline
sent to a covid 19 unit & 7\tabularnewline
sent to a covid 19 icu & 1\tabularnewline
\textbf{warfarin/heparin at discharge} & 17\tabularnewline
COPD: chronic obstructive pulmonary disease, cad: coronary artery
disease, lvd: left ventricular dysfunction, iabp: intra-aortic balloon
pump & COPD: chronic obstructive pulmonary disease, cad: coronary artery
disease, lvd: left ventricular dysfunction, iabp: intra-aortic balloon
pump\tabularnewline
\bottomrule
\end{longtable}

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