key: cord-0997422-2xoczdmh
authors: Tolba, Marwa; Abo Omirah, Marwa; Hussein, Amal; Saeed, Haitham
title: Assessment and Characterization of Post‐COVID‐19 manifestations
date: 2020-09-29
journal: Int J Clin Pract
DOI: 10.1111/ijcp.13746
sha: f24c835bc06e10ae32936afecc6a183bea973140
doc_id: 997422
cord_uid: 2xoczdmh

BACKGROUND: Post COVID‐19 symptoms and diseases appeared on many survivors from COVID‐19 which are similar to that of the post‐severe acute respiratory syndrome (SARS) fatigue. Hence, the study aims to investigate and characterize the manifestations which appear after eradication of the coronavirus infection and its relation to disease severity. METHOD: 287 survivors from COVID‐19 were included in the study, each received a questionnaire divided into three main parts starting from subjects’ demographic data, data about the COVID‐19 status and other comorbidities of the subject, and finally data about post‐COVID‐19 manifestations. Response surface plots were produced to visualize the link between several factors. RESULTS: Only 10.8 % of all subjects have no manifestation after recovery from the disease while a large percentage of subjects suffered from several symptoms and diseases. The most common symptom reported was fatigue (72.8 %), more critical manifestations like stroke, renal failure, myocarditis, and pulmonary fibrosis were reported by a few percent of the subjects. There was a relationship between the presence of other comorbidities and severity of the disease. Also, the severity of COVID‐19 was related to the severity of post‐COVID‐19 manifestations. CONCLUSION: The post‐COVID‐19 manifestation is largely similar to the post‐SARS syndrome. All subjects recovered from COVID‐19 should undergo long‐term monitoring for evaluation and treatment of symptoms and conditions that might be precipitated with the new coronavirus infection.

Coronavirus disease 2019 (COVID-19) is a serious respiratory disease that resulted from infection with a new coronavirus (SARS-COV-2). One of the most critical issues related to the COVID-19 is the high spread rate, millions of people have been infected around the world, and hundreds of thousands of deaths till now had been recorded. Patients suffered from different symptoms like fever, dry cough, and fatigue which is mild in about 80% of cases, but the severity of the case may progress to develop a respiratory distress or respiratory failure and hence the need for intensive care unit (ICU) will be increased [1] . The severity of the disease is related to age and comorbidities of the infected subjects; the elderly are severely affected with the need for ICU [2] . The severity of symptoms is also related to its duration, for mild cases, symptoms may last for 2 weeks while for the severe cases it ranges from 3 to 6 weeks [3] . Direct contact to confirmed cases is the main way by which the disease transfer among people because the SARS-COV-2 is transmitted through exhaled air and aerosol [4] .

Diagnosis of COVID-19 is done through polymer chain reaction (PCR), computed tomography (CT) scan, and blood test [5] . For mild cases, supportive treatment is the only choice including antibiotics, vitamins, trace elements, and antipyretics, while those with respiratory distress, the oxygen therapy with or without mechanical ventilation should be introduced and individualized according to each case [6] . A lot of medications were included in clinical trials to act as antiviral but there are no clear results to indicate the confirmed effect for any of the investigated medications [7] [8] [9] . In addition to symptomatic therapy, corticosteroids as an anti-inflammatory could play a vital role in severe cases [10] . Most of the infected patients have recovered from the disease, this recovery could be confirmed by another PCR or by the absence of the symptoms for several days. However, many cases have suffered from different symptoms after recovery from the disease which are different from COVID-19 symptoms [11] . Post recovery manifestations were also studied after the severe acute respiratory syndrome (SARS) attack in 2003 reflecting many symptoms experienced by studied subjects such as fatigue, myalgia, depression, and weakness [12] . Some of these manifestations were chronic and lasted for a long time which required long term monitoring [12] . In addition to the previously

This article is protected by copyright. All rights reserved mentioned mild symptoms, a mild hypoactivation of the hypothalamic-pituitary-adrenal axis was reported by Leow et al [13] . Hence the current study aims to investigate the post-COVID-19 manifestation to demonstrate the different symptoms or signs that appeared on subjects after recovery from the disease, also to link these symptoms with several factors (age, weight, disease severity, or other comorbidities).

Recovered Egyptian subjects from COVID-19 received a questionnaire aimed to collect data related to their post-COVID-19 manifestations. This questionnaire was divided into several parts starting from subjects' demographic data (age, gender, height, smoking, and weight), then data about the The study involved 287 recovered COVID-19 subjects, 103 of them were males and 184 females.

Age of involved subjects expressed as Mean ± SD was 32.3 ± 8.5 and ages ranged from 20 to 60 years

This article is protected by copyright. All rights reserved old. Mean ± SD weight, height, and body mass index (BMI) were 77 ± 16.4, 162.9 ± 15.3, and 28.5 ± 5.2 respectively. Percent of smokers among male subjects was 27.2 %, while all females were nonsmokers. Regarding other diseases, 70.7 % of all subjects have no known history of other illnesses, while 7.7 % have hypertension and 5.2 % were diabetic. The severity of COVID-19 symptoms was divided into three categories, first is the mild cases that were isolated at home and they expressed 80.2 %, the second category was the moderate cases that received oxygen therapy and they represent 14.9 %, the third category was the severe cases that required ICU admission and this category represent a small percent (4. The severity of COVID-19 was related to age and comorbidities as shown in figure 1 . Also, the severity of post-COVID-19 manifestations was related to the severity of COVID-19 ( Figure 2 ).

Post COVID-19 manifestations were recorded for about 90 % of the recovered subjects, with a wide range of symptoms and conditions that varied from a low-critical symptom like a headache to more critical conditions such as stroke, renal failure, and pulmonary fibrosis. Post viral infection syndrome was previously reported after SARS [12, 13] . Follow up for 4 years showed that chronic fatigue and psychiatric conditions continued to be clinically significant among subjects survived from SARS infection [14] . Hence, mental health morbidities management should be optimized through a multidisciplinary approach combined with long-term rehabilitation. Regarding COVID-19 survivors,

This article is protected by copyright. All rights reserved each subject reported one or more manifestations, those manifestations persisted with all subjects for more than 20 days from the last negative PCR. The severity of COVID-19 was classified into three categories as follow; mild cases that had controllable symptoms and have been treated at home without the need for oxygen therapy, moderate cases which suffered from difficult breathing and needed oxygen therapy at home, and severe cases that had been hospitalized and needed ICU. The relation between age, comorbidities, and severity of COVID-19 showed a strong link between the presence of other comorbidities and the severity of COVID-19 [15] . Also increasing age was related to increased severity of the disease course [16] . Most of the reported manifestations were mild reversible symptoms that could be relieved without medical interventions such as fatigue and headache which could be related to COVID-19 symptoms. Other mild symptoms like joint and muscle pain were also reported by many subjects and it could be classified as mild manifestations. It was noted that many manifestations are related to the central nervous system such as continuous headache, migraine, depression, anxiety, and obsessive-compulsive disorder. Few percent of subjects have suffered from critical complications such as stroke, myocarditis, renal failure, and pulmonary fibrosis which could be reversible and required extra investigation. Regarding obesity as a factor affecting disease severity or post disease symptoms, it was shown that the majority of subjects were overweight or obese but there is no significant effect on the severity grade or type of post-COVID-19 symptoms. The manifestation of post-COVID-19 that have been recorded during this study could be classified as mild or critical, the critical manifestations are those affecting organ functions such as pulmonary fibrosis, renal failure, myocarditis, arrhythmia, and stroke. There was a relationship between the severity of post-COVID-19 manifestations and the severity of the disease, the severe cases expressed high severity manifestations compared with those suffering from mild condition [11] .

Hence, the severity of manifestations is also related to the age and comorbidities of the involved subjects. All cases with severe manifestations have confirmed their diagnosis through laboratory investigations and imaging procedures such as CT scan for diagnosis of pulmonary fibrosis. The most-reported manifestation for this study was fatigue which also reported by Tansey et al. after SARS in 2003 [17] . Fatigue persisted with recovered subjects from SARS for several months, as subjects were monitored every 3 months, more than 50 % of subjects were suffering from fatigue each time [17] . Another study followed up SARS subjects for 4 years to evaluate the percent of chronic Accepted Article fatigue in those subjects and they found that about 40.3 % suffered from chronic fatigue [14] . In addition to fatigue, neuropsychiatric symptoms were documented for a large percent of COVID-19 subjects, also this finding could be consistent with Lara et al. finding after monitoring neuropsychiatric symptoms of Alzheimer's and mild cognitive impaired subjects whose were infected For subjects recovered from COVID-19, negative PCR is not the end of patient monitoring, continuous and long-term monitoring of the subjects is recommended for evaluation of post-COVID-19 manifestation, and early intervention with the critical signs. Also, the need for continuous counseling with the subjects is very important not only for maintaining good adherence to the medications, but also for detection of early warning signs of developing serious manifestations.

Adherence to medications has a beneficial effect on patient's outcomes [23] .

Most of the subjects recovered from COVID-19 experienced several manifestations after the last negative PCR which could be mild symptoms such as fatigue, headache, or more critical manifestations like pulmonary fibrosis, stroke, and myocarditis. The most reported symptoms were

This article is protected by copyright. All rights reserved fatigue, anxiety, joint pain, and headache. The severity of post-COVID-19 manifestations was correlated to the severity of the infection which also was related to the presence of comorbidities. The post-COVID-19 manifestation is largely similar to the post-SARS syndrome. All subjects recovered from COVID-19 should undergo long-term monitoring for evaluation and treatment of symptoms and conditions that might be precipitated after recovery from the new coronavirus infection. 

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