COVID-19: Post-recovery long-term symptoms among patients in Saudi Arabia.

BACKGROUND: After recovery from acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many patients experience long-term symptoms in different body systems. The aim of the present study was to identify these symptoms, their severity, and their duration as a first step in building a system to classify post-recovery long-term symptoms of coronavirus disease 2019 (COVID-19).
METHODS: An online-based cross-sectional survey was administered between September and October 2020. Data regarding the severity of post-recovery symptoms and their duration were collected using an Arabic questionnaire divided into six categories encompassing the 20 most prevalent symptoms.
RESULTS: A total of 979 patients recovered from COVID-19 in Saudi Arabia in the study period, of whom 53% were male and 47% were female. The most common symptoms included general fatigue and weakness (73% each), with moderate severity of neurological symptoms including mood changes (41%) and insomnia (39%). Among the special senses, loss of smell and taste of marked severity were reported by 64% and 55% among respiratory symptoms, cough of mild severity (47%), and dyspnea of moderate severity (43%). Loss of appetite of moderate severity was reported in 42%, and diarrhea, abdominal pain, and nausea of mild severity were reported by 53%, 50%, and 44% of respondents, respectively.
CONCLUSIONS: Long-term symptoms after recovery from COVID-19 warrant patient follow-up. The authors propose a classification system as a starting point to guide the identification and follow-up of long-term symptoms post-recovery, and recommend larger-scale studies to broaden the definition of recovery from COVID-19, which appears to have two phases, acute and chronic.

Introduction

An outbreak of a novel coronavirus, putatively termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), occurred in the city of Wuhan, China in December 2019 [1]. In March 2020, the World Health Organization declared the outbreak a pandemic. The identified virus, SARS-CoV-2, is similar to other fatal coronaviruses, namely SARS-CoV and Middle East Respiratory Syndrome coronavirus [2,3].

Coronavirus infection commonly causes respiratory and gastrointestinal symptoms; similarly, SARS-CoV-2 infection also leads to such symptoms, mainly fever, generalized weakness, lower respiratory tract symptoms, and anosmia caused by severe lung injury and acute respiratory distress syndrome, and affects multiple organs possibly causing organ failure, especially in old patients (>60 years) patients and/or those with specific comorbidities, which suggests that COVID-19 should be considered a systemic disease [4-6].

Many studies and reviews have focused on systems affected other than the respiratory system, including neurological, cardiac, vascular, gastrointestinal, kidney, and cutaneous manifestations [7-17]. Aside from the acute clinical challenges in those with severe illness, the long-term sequelae of pneumonia have been reported in many studies focusing on the decline in quality of life after pneumonia diagnosis that did not return to baseline—even after 1 year—and persistent late psychological effects, alongside the implications for rehabilitation and health care utilization [18-21]. The long-term effects of viral pneumonia among survivors, including those infected with SARS and MERS, have been documented. The same has been observed in those who recovered from COVID-19, in which survivors of acute illness experience long-term symptoms that persist for varying periods and varying degrees of severity. However, there are only a limited number of studies that followed patient symptoms after recovery from acute illness with COVID-19, and most focused on only one or a few symptoms, such as anosmia and cardiac conditions [22-27]. These symptoms impose a burden on patient health [28], and also affect physical and social status [29,30], which in turn have adverse effects on virtually all aspects of human activity and contribute to high burden on the economy and society. The pathogenesis of these post-recovery, long-term symptoms of COVID-19 remains unclear. As such, there is an urgent need to categorize these long-term symptoms according to the severity of their impact. This will raise awareness of the urgent need for studies to determine the underlying pathogenesis of the disease to better understand the process and, secondarily, for proper planning for patient management.

To date, published studies have focused on only one or a few symptoms, and have been smaller-scale investigations, which may increase the risk for missing other symptoms that lead to more serious longer-term effects on patients. Accordingly, the aim of the present study was to survey a larger number of patients who recovered from acute infection and illness with SARS-CoV-2/COVID-19 using different variables and an adequate number of post-recovery symptoms as a first step in building a classification system for COVID-19 post-recovery symptoms according to significance of importance, which should provide an opportunity for deeper understanding and future research to fill important knowledge gaps.

Materials and methods

Study design

Ethical approval for this study was obtained from the Subcommittee of Health Research Ethics, Deanship of Scientific Research, Qassim University (ref. # 20-03-04) and informed consent was obtained from all participants during the online-based cross-sectional survey. A survey was administered between September and October 2020 using Google Forms and Twitter as a forum, an anonymous Arabic survey was distributed. Saudi nationals and residents who had been recorded to be recovered from acute COVID-19 symptoms have been included in the study. There were no monetary benefits and participation was purely voluntary. Participants were told about the purpose of the questionnaire, the sample, and the significance of the score for each answer on the survey’s landing page, and were required to provide informed consent before proceeding to respond to the items. Participants were thanked for their participation on the final page. A new Twitter account was used to recruit the participants. Individuals and organizations received “tweets” requesting that they “retweet” the survey connection. According to Internet protocol restrictions, multiple enrolments by the same individual were prohibited.

Instrument development

The questionnaire used in this study was created using a combination of published literatures [31-35] and internal discussion among the research team to assess question format, comprehensiveness, clarity, and flow. Participants were assured that their responses would be collected anonymously, reducing the potential for bias introduced by self-reported results. The questionnaire was created and required approximately 3–5 minutes to complete with the aim of reducing survey fatigue. It was tested for validity using face validation by the survey research experts. The questionnaire was written in English by a native English speaker and translated into Arabic by two native Arabic speakers. The Arabic version of the questionnaire was piloted and distributed.

Instrument measures

The model was conducted on a group of 40 recovered COVID-19 cases in order to optimize the wording and clarification of the survey questions. The survey was widely distributed after slight changes to the format and vocabulary. The results of the pilot study were not included in any subsequent research but used for construct validity by employing the Pearson’s correlation coefficient r of the scores of respondents’ responses to an item with their total scores. According to the classification of r values as previously reported [36], the results showed that none of the questions presented poor correlations. All questions showed positive correlation that ranged from fair to very strong with significant relationships (Pearson’s r = 0.34–1.00; p<0.05). The instrument’s reliability was verified through Cronbach’s alpha as described in previously [37] by calculating the existing correlations. The result of this test was 0.870, which reflected a strong internal consistency. Final questionnaire was structured into 6 sections addressing specific symptoms potentially correlated with SARS-CoV-2 infection/COVID-19 as follows: (I) General symptoms (2 items: fatigue and weakness); (II) Skin and musculoskeletal symptoms (3 items: muscle ache[s], joint pain, and skin rash); (III) Psychological and neurological symptoms (4 items: headache, mood changes, insomnia, esthesia, and anesthesia); (IV) Special sense symptoms (5 items: hearing problems, visual disturbances, dry eyes, loss of smell, and loss of taste); (V) Respiratory system symptoms (3 items: cough, shortness of breath, and chest tightness); and (VI) Gastrointestinal symptoms (4 items: lack of appetite, nausea, diarrhea, and abdominal pain). Each section consisted of a group of related symptoms. For each symptom, participants were asked to score the severity of each on a three-point scale (mild, moderate, and severe, scored as 1, 2, and 3, respectively), and to report the duration of persistence of this symptom(s) after recovery in days. More than one symptom could be reported. Information regarding participant demographics and the method of diagnosis of SARS-CoV-2 infection was collected.

Sample size calculations

The estimated sample size was 384, which was obtained by a statistical calculation from the official Saudi Ministry of Health records, announced the number of recovered cases with a 95% confidence level and a 5% margin of error. We applied the online survey from September to October 2020 and a total of 992 Saudi subjects were approached. Out of them, 979 were included and the rest 13 subjects were omitted as they were made invalid selection. As reported previously [38,39], that sample size of 500 is very good, and 1000 or more is excellent, larger samples are always better than smaller, therefore it is recommended to utilize as large a sample size as is possible. Applying the same principle, 979 Saudi nationals were recruited in the study.

Data management and statistical analysis

The datasets were processed and analyzed using the PivotTable, data analysis within Microsoft excel version 2019. Descriptive statistics such as frequencies, percentage, mean and standard deviation (SD) were employed for the presentation of categorical and continuous variables to summarize respondent characteristics. Moreover, the data were further verified by SPSS version 25.0 (IBM Corporation, Armonk, NY, USA) using ANOVA and LSD tests. Differences with p ≤ 0.05 were considered to be statistically significant. Bar graphs were plotted for different variable including the age groups, methods of diagnosis, gender proportion and average days for each of the COVID-19 post recovery long-term symptoms.

Results

Of the 979 patients recovered from COVID-19, as they were post recovery group so none were experiencing acute symptoms or fever at the time the survey was administered. The males and females respondents in the study were 53% and 47%, respectively. Characteristics of the study population are summarized in Table 1. The frequency, degree of severity, and persistence of symptoms (in days) after recovery are summarized in Tables 2 and 3, and Figs 1–3. The largest age group comprised individuals 20 to 39 years of age (57.1%), with a mean age of 37.69. The most common long-term (i.e., persistent) symptoms were of general symptoms group, fatigue and weakness (73% each), which persisted for a mean of 7 and 8.11 days respectively, while muscle aches were the dominant symptom (66%) among the skin and musculoskeletal symptom groups, with a mean persistence of 7.8 days. Among psychological and neurological symptoms, headache was the most common (64%), with a mean persistence of 6.5 days. The presenting symptom among the special sense group was loss of smell (62%), with a mean persistence of 15.9 days (Table 2). Cough was the dominant symptom (47%) in the respiratory system group, and lack of appetite (46%) was the dominant symptom in the gastrointestinal group, with a mean persistence of 11 days and 9.4 days, respectively (Table 2). The most severe degree of symptom was scored “3”, which was recorded for both loss of smell and loss of taste, which also demonstrated the highest mean duration of symptom persistence (15.9 and 13.9 days, respectively) (Table 3). To study these findings in depth, we further categorized the studied cases in four age groups (Table 1). We observed a significant correlation of post-recovery COVID-19 symptoms with age, persistence of symptoms and degree of severity. Furthermore, we also found a statistically significant relation of age with the presence of post-recovery COVID-19 long term symptoms degree of severity and/or persistence, such as weakness degree (p = 0.003), persistence (p = 0.001), lack of appetite degree (p = 0.02), persistence (p = 0.003), Insomnia degree (p = 0.01), loss of smell degree (p = 0.002), loss of taste degree and Headache degree (p = 0.04 each), cough degree (p = 0.01) significant correlation was found between age and persistence of symptoms as fatigue (p = 0.004), joint pains (p = 0.01), mood changes (p = 0.03), nausea (p = 0.002) and abdominal pain (p = 0.02; Tables 2 & 3). According to the findings we proposed a scoring system that can be can be delivered online for post discharge follow-up, and the score of each case can be automatically calculated. The case that will reach the proposed score should be invited for follow up in the clinic, keeping in mind high concerns groups (as in Table 4 level 1A&B) should be the first priority follow up group, while lower concerns groups (as in Table 5 level 2 A&B) should be the second priority follow up. The cases will not reach the proposed score, no need for clinic follow up and should be reassured as mostly their symptoms are self-limited. By this scoring system we can easily pick up patients of concern to be followed up and also decrease load on health services as much as possible.

Table 1

Demographic and clinical characteristics of the study individuals.

Characteristics	Value
Age, years (y)—mean (±SD)	37.69 (±10.77)
Minimum	10 y
Maximum	84 y
Gender	Number of subjects (N) (%)
Male	519 (53%)
Female	460 (47%)
Method of diagnosis	N (%)
Swab only	117 (12%)
Symptoms only	158 (16%)
Swab & Symptoms	704 (72%)
Age groups by years	N (%)
10–19	31 (3.2%)
20–29	177(18.1)
30–39	383(39.1%)
40–49	241(24.6%)
50–59	113(11.5%)
60–69	30 (3.1%)
70–79	3 (0.3%)
80–89	1(0.1%)
Age group categories	N (%)
>20 y	32 (3.3%)
20–39 y	559 (57.1%)
40–59 y	354 (36.2)
60 and above	34 (3.5%)

Table 2

Persistence days of post-recovery of COVD-19 recorded symptoms in 979 studied subjects.

	Descriptive Statistics	Mean (days)	Median (days)	Standard Deviation	Range (days)	No.	%	p-value
I-General Symptoms	Fatigue Days	7	5	8.6	120	719	73%	0.004*
	Weakness Days	8.1	5	9.8	119	715	73%	0.001*
II- Skin and Musculoskeletal symptoms	Muscle aches Days	7.8	5	12	119	646	66%	0.14
	Joint pains Days	7.2	5	9.4	119	595	61%	0.01*
	Skin Rash Days	5.4	2	11.7	119	164	17%	0.62
III- Psychological and Neurological symptoms	Headache Days	6.5	4	8.2	119	627	64%	0.73
	Mood changes Days	9.5	7	11.9	154	501	51%	0.03*
	Insomnia Days	8.8	7	10.6	89	432	44%	0.21
	Paraesthesia and anesthesia Days	7	4	11.1	119	296	30%	0.85
IV- Special sense symptoms	Hearing problems Days	7.5	5	11.9	119	129	13%	0.94
	Visual disturbances Days	7.3	4	9.9	59	145	15%	0.40
	Dry eyes Days	7.9	5	11	63	185	19%	0.88
	Loss of smell Days	15.9	10	19.5	149	604	62%	0.63
	Loss of taste Days	13.9	9	16.6	119	555	57%	0.60
V- Respiratory system symptoms	Cough Days	11	7	12.8	120	457	47%	0.09
	Breathlessness and chest tightness Days	9	6	10.7	119	388	40%	0.45
VI- Gastrointestinal symptoms	Lack of appetite Days	9.4	7	8	59	455	46%	0.003*
	Nausea Days	6.9	5	7	59	313	32%	0.002*
	Diarrhea Days	6.4	4	8.8	119	402	41%	0.42
	Abdominal pain Days	6	4	6.6	44	253	26%	0.02*

*p<0.05 considered statistically significant. P values were calculated by ANOVA and LSD tests using SPSS software.

The mean (±SD) age of the subjects was 37.69 (±10.767) years.

Table 3

Degree of severity of the recorded post recovery COVD-19 long-term symptoms with their frequency of expression.

		Degree of severity and its frequency of expression				p-value*
Symptoms groups	Long term recorded symptom	Mild N (%)	Moderate N (%)	Severe N (%)	No.
I-General Symptoms	Fatigue	239 (33%)	326(45%)	154(21%)	719	0.05
	Weakness	254(36%)	328(46%)	133(19%)	715	0.003*
II- Skin and Musculoskeletal symptoms	Muscle aches	208 (32%)	279(43%)	159(25%)	646	0.36
	Joint pains	232(39%)	220(37%)	143(24%)	595	0.44
	Skin Rash	142(87%)	17(10%)	5(3%)	164	0.86
III- Psychological & Neurological symptoms	Headache	195(31%)	242(39%)	190(30%)	627	0.04*
	Mood changes	166(33%)	216(43%)	119(24%)	501	0.20
	Insomnia	157(36%)	171(40%)	105(24%)	432	0.01*
	Paraesthesia and anesthesia	167(56%)	96(32%)	33(11%)	296	0.25
IV- Special sense symptoms	Hearing problems	95 (74%)	23(18%)	10(8%)	129	0.41
	Visual disturbances	108(75%)	25(17%)	12(8%)	145	0.34
	Dry eyes	108(58%)	59(32%)	18(10%)	185	0.01*
	Loss of smell	95(16%)	124(21%)	385(64%)	604	0.002*
	Loss of taste	95(17%)	152(27%)	308(55%)	555	0.04*
V- Respiratory system symptoms	Cough	215(47%)	149(33%)	93(20%)	457	0.01*
	Breathlessness and chest tightness	159(41%)	166(43%)	63(16%)	388	0.42
VI- Gastrointestinal symptoms	Lack of appetite	138(30%)	191(42%)	126(28%)	455	0.02*
	Nausea	137(44%)	108(34%)	68(22%)	313	0.22
	Diarrhea	212(53%)	120(30%)	70(17%)	402	0.69
	Abdominal pain	127(50%)	103(41%)	23(9%)	253	0.83

*p<0.05 considered statistically significant. P values were calculated by ANOVA and LSD tests using SPSS software.

The mean (±SD) age of the subjects was 37.69 (±10.767) years.

Fig 1

Age groups and gender proportion for recovered COVID-19 patients.

Fig 3

Degree of severity and frequency expression for different COVID-19 post recovery long term symptoms.

Table 4

(Level-1 A): Scoring Post-recovery COVID-19 long term symptoms persistence (High concerns groups). Scoring method: One point given for each item per symptom (one point for days and one point for age group). Interpretation: Score two for any symptom: follow up is recommended for the patient for each symptom got score 2. (Level 1 B): Scoring Post-recovery COVID-19 long term symptoms degree of severity (High concerns groups). Scoring method: One point given for each item per symptom (one point for severity and one point for age group). Interpretation: Score two for any symptom: follow up is recommended for the patient for each symptom got score 2.

Long term symptom	Days (≥) *	Age groups (years, y)
Fatigue	5	≥41
Weakness	5	≥40
Joint pains	5	≥20
Mood changes	7	20-59y
Lack of appetite	7	20-59y
Nausea	5	20-59y
Abdominal pain	4	20-59y
Long term symptom	Degree of severity (≥) **	Age group
Fatigue	2	Any age group*
Weakness	2	Any age group*
Headache	2	20-59y
Insomnia	2	<20y or ≥ 40 y
Dry eyes	1	20–39 or ≥60y
Loss of smell	3	20–39 or ≥40y
Loss of taste	3	10-39y
Cough	1	<20y or 40–59 y
Lack of appetite	2	<20y or ≥40y

*Days here are the recorded median number for each symptom.

*Cases age between 10–84 years.

**Degree of severity Mild = 1, Moderate = 2, Severe = 3.

Table 5

(Level 2 A): Scoring Post-recovery COVID-19 long term symptoms persistence (Lower concerns groups). Scoring method: One point given for each item per symptom (one point for days and one point for age group). Interpretation: Score two for any symptom: follow up is recommended for the patient for each symptom got score 2. (Level 2 B): Scoring Post-recovery COVID-19 long term symptoms degree of severity (Lower concerns groups). Scoring method: One point given for each item per symptom (one point for degree of severity and one point for age group) with exception for loss of smell and loss of taste. Interpretation: Score two for any symptom: follow up is recommended for the patient for each symptom got score 2.

Long term symptom	No. of days (≥) **	Age group (years)
Fatigue	7	10-39y
Weakness	8	10-39y
Muscle aches	8	Any age group*
Joint pains	7	<20y
Skin Rash	5	Any age group*
Headache	7	Any age group*
Mood changes	10	<20y or ≥60y
Insomnia	9	Any age group*
Paraesthesia and anesthesia	7	Any age group*
Hearing problems	8	Any age group*
Visual disturbances	7	Any age group*
Dry eyes	8	Any age group*
Loss of smell	16	Any age group*
Loss of taste	14	Any age group*
Cough	11	Any age group*
Breathlessness and chest tightness	9	Any age group*
Lack of appetite	10	<20y or ≥60y
Nausea	7	<20y or ≥60y
Diarrhea	6	Any age group*
Abdominal pain	6	<20y or ≥60y
Long term symptom	Degree of severity **	Age group (years)
Muscle aches	>2	Any age group*
Joint pains	>1	Any age group*
Skin Rash	>1	Any age group*
Headache	>2	<20y or≥60y
Mood changes	>2	Any age group*
Insomnia	>2	20-39y
Paraesthesia and anesthesia	>1	Any age group*
Hearing problems	>1	Any age group*
Visual disturbances	>1	Any age group*
Dry eyes	>1	<20y or 40-59y
***Loss of smell	3 in severity plus 9.7 days****	<20y
***Loss of taste	3 in severity plus 12 days****	≥40y
Cough	>1	20-39y or ≥60y
Breathlessness and chest tightness	>2	Any age group*
Lack of appetite	>2	20-39y
Nausea	>1	Any age group*
Diarrhea	>1	Any age group*
Abdominal pain	>1	Any age group*

*Cases age between 10–84 years.

**Days here are the average number of days recorded for each symptom.

*Cases age between 10–84 years.

**Degree of severity Mild = 1 Moderate = 2 Severe = 3.

****Degree plus persistence duration got one point.

****Days here are the average number of days for the mentioned age group.

Discussion

To our knowledge, the present study is the first to describe the duration and severity of symptoms among individuals in Saudi Arabia following infection with SARS-CoV-2 and subsequent illness with COVID-19. This study was designed to address post-recovery symptoms in patients who experienced acute symptoms of COVID-19.

Twenty symptoms were included in the questionnaire and covered general symptoms, and skin, musculoskeletal, neurological and psychological symptoms. Fatigue, and weakness of moderate severity were the most commonly reported general symptoms (73% each), with a mean duration of 7 days for fatigue; however, symptoms of weakness persisted longer, with a mean duration of 8.1 days. These symptoms are usually observed in recovering patients with respiratory tract infections among old age (>60 years) patients, or after lengthy hospital stay or critical illness [40-45].

More than 80% of our participants comprised a relatively young age group (20 to 50 years) with good health status before contracting COVID-19, which indicates that weakness and fatigue are significant post-recovery symptoms of COVID-19, and is consistent with other studies that described fatigue as a long-term symptom and one of several common sequelae of COVID-19. Moreover, it is independent of the severity of the previous acute illness or levels of pro-inflammatory markers [46]. Muscle ache(s) of moderate severity and joint pain of mild severity were reported by 43% and 39% of respondents, respectively. Myalgia during the acute stages of COVID-19 has been well documented [47], ranging from 11% to 44% in other studies [48,49], and myalgia and arthralgia were also evident in various other coronavirus infections during acute illness [50].

The persistence of myalgia and arthralgia after acute illness may reflect the activation and triggering of excessive or uncontrolled cytokine responses, and a local inflammatory reaction in the respiratory tract, especially the alveoli, which progresses to involve other organs, especially the joints and muscles [51].

Neurological complications have also been studied in individuals infected with other human coronaviruses. Neuro-invasion causing neurological pathologies ranging from headache and anosmia to severe and fatal encephalopathy, encephalitis acute myelitis, Guillain-Barré syndrome, and other cerebrovascular pathologies have been documented [52].

In the present study the post-COVID-19 headache was reported by 64% of our participants, it was of moderate severity among 39% and persisted for a mean of 6.5 days, whereas anosmia was reported in severe degree by 64% and persisted for a mean of 15.9 days. Headache is considered one of the characteristic and cardinal symptoms of COVID-19, and is observed in 68.3% of patients in the emergency department [53]. Other symptoms addressed in our survey included mood changes of moderate degree in 43% and paresthesia in 56% of mild cases.

Anosmia is currently considered a cardinal and prominent symptom of COVID-19 [54,55], and may be the only presenting symptom [56] and is commonly associated with loss of taste (dysgeusia) [57]. Anosmia results from damage to the olfactory epithelium or, more commonly, the central olfactory pathway [58]. It has been observed in previous human coronavirus infections; however, the incidence is higher with SARS-CoV-2 infection [59]. Some cross-sectional studies have reported anosmia incidences ranging from 33.9% to 68% [60-63]. Among 114 swab-positive patients, Klopfenstein et al. [60] reported an anosmia incidence rate of 47%, with a mean duration of 8.9 days.

In this study, the incidence of anosmia was 62%, with a mean duration of 15.9 days and 64% of cases are of severe degree while the incidence of loss of taste was 57%, with a mean duration of 13.9 days and 55% of cases are of severe degree.

The higher percentages and longer durations found in our study may be attributed to mutations of SARS-CoV-2, which result in different genotypes and pathogenicity [61]. Other factors may be related to the currently increased awareness of anosmia in patients with COVID-19 compared to early in the outbreak. Another reason may be related to the varying pathogenicity of SARS-CoV-2 among humans; however, this remains speculative and needs more supportive evidence. In fact, the incidence of anosmia was as high as 98% in a study by Moein et al., who performed specific olfactory testing in patients positive for COVID-19, and identified a high percentage of patients (63%) who were unaware of their anosmia [62]. Other sensory effects include hearing and visual disturbances (17% and 19%, respectively), which are rarely investigated in those with acute COVID-19 illness. To the best of our knowledge, this is the first investigation to include patients who recovered from COVID-19.

Respiratory symptoms that persisted after acute illness included cough of mild severity (47%, with a mean duration of 11 days) and dyspnea of moderate severity (43%, duration 9 days). In 2020, a study by Garrigues et al. investigating discharged patients with COVID-19 found that the incidence of dyspnea was 42% and there was no difference between those admitted to the intensive care unit and general ward [63]. Gastrointestinal symptoms were significant in our study for lack of appetite (42%), with a mean duration of 9.4 days (moderate severity), while other symptoms, such as nausea (44% [6.9 days]), diarrhea (53%, [6.4 days]), and abdominal pain (50% [6 days]), were all mild.

To our knowledge, this is the first study to investigate post-recovery gastrointestinal symptoms in those with COVID-19. Most centers and hospitals considered COVID-19 case recovered by subsidence of acute symptoms. Follow up of hundreds of thousands of recovered cases is not practical and will add much extra load on health services which are barely coping with acute cases. Furthermore, we aren’t able to anticipate which patients will suffer long-term symptoms following their recovery, and if so, does all long-term symptoms cases need follow up. As our study highlights the importance of follow-up of patients who recover from acute illness to identify those who may be more likely to experience long-term symptoms that may require further care and investigation. To solve this issue, we proposed a scoring system for COVID-19 post recovery long-term persistent symptoms according to the degree of severity and the duration of persistence, which is best known to our knowledge, is the first time all over the world to classify and score COVID-19 post recovery long term symptoms (Tables 4 and 5).

Limitations

This study has few limitations including lack of knowledge of the severity of initial illness, details regarding hospitalization, obstacles to meet all survey participants, and the lack of a control group. In addition, the questionnaire used in this study has four limitations: (1) The first obvious one was the respondent’s previous experience filling out questionnaires may have an impact on the overall outcome, (2) who completed the questionnaires? The respondent or the surveyor, (3) to receive truthful responses from respondents who fill out the questionnaires, (4) the ways of online administration of the questionnaire such as Google and Twitter forums. In comparison to an interview room, an on-site survey may generate distraction owing to noise and task.

Conclusions

This study confirmed that the long-term persistent symptoms are evident among individuals who recover from COVID-19. This should raise awareness of the importance of post-recovery follow-up of cases to manage persistent symptoms and reduce the burden on patients and the community. Further studies, however, are needed to investigate the pathogenesis of these persistent symptoms. As we recorded long term persistent symptoms with different degrees of severity and variable persistence, we propose to classify COVID-19 illness into two phases: acute and chronic so we can consider long term persistent symptoms after recovery from acute illness and not to miss any case. Our proposed scoring system will encourage wider scale studies to confirm and refine the findings by considering geographical distribution and a larger number of COVID-19 cases. This will help to identify priorities in follow-up among patients according to our proposed scoring system and to avoid prolonged suffering in those who considered recovered from COVID-19 “acute illness”.

(XLSX)

Click here for additional data file.

The English and Arabic versions of the questionnaire used in the study.

(DOCX)

Click here for additional data file.

31 Mar 2021

PONE-D-21-02645

COVID-19: Post recovery long-term symptoms among patients in Saudi Arabia

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Additional Editor Comments (if provided):

Dear Authors, thank you for submitting in Plos One. Your manuscript has been assessed by relevant experts from the field. They found manuscript interesting but raised some concerns in methodology (study instrument validation and translation, sampling technique and methods of recruitment) and interpretation of results. It is requested to please consider the comments of reviewers.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: No

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: In their paper COVID-19: Post recovery long-term symptoms among patients in Saudi Arabia, Khodeir et al aimed to identify long-term symptoms in different body

systems symptoms following COVID-19, their severity, and their duration as a first step in building a system to classify post-recovery long-term symptoms of coronavirus disease 2019 (COVID-19). They conclude that Long-term symptoms after recovery from COVID-19 warrant patient follow-up. The authors propose a classification system as a starting point to guide the identification and follow-up of long-term symptoms post-recovery, and recommend larger-scale studies to broaden the definition of recovery from COVID-19, which appears to have two phases, acute and chronic.

While the goal of this paper is interesting, several improvements can be made to this paper:

1. The methods sections requires expansion, a copy of the questionnaire, its translation etc needs to be placed in the methods.

2. The statistics portion requires more sophisticated analysis. For example, usually the mean is reported with SD, and the median is reported with the interquartile range and/or range. Here the authors report the mean SD and range. Also, to develop a score or classification system, there has to be an end point. For example, what is the goal of this classification? Is there a stage? Is there a score? Is one type better than the others. Several adjustments of baseline characteristics are needed. Saudi versus non-Saudi is not needed, Race, ethnicity, work, etc. may be better. LOTS of improvement may be made to this section

3. The results section needs more details. I think reporting the “classification system” reposting a “scale for it” briefly reporting the populations. Again, improvements need to be made

4. The tables could become one table

5. Figures would help deliver the message better

6. The conclusion is too long, and should not have references or references to tables, this should move to the discussion. The conclusion summarizes your findings, not others.

In summary, while the findings and goal of the study is quite good, the structure of this paper could improve.

Reviewer #2: In the manuscript authored by Mostafa Khodeir et al, the authors reported results obtained from an on-line survey about the post recovery long-term symptoms among patients in Saudi Arabia. Despite manuscript is valuable in the attempt here below I reported my comments and suggestions:

-It is not clear in the method section how subjects have been included. Authors stated: "The estimated sample size was 663, which was obtained by statistical calculation from the official Saudi Ministry of Health website, which announced the number of recovered cases with a 99% confidence level and a 5% margin of error". Thus, why authors did not contacted directly those 663 persons? It is correct the 99% confidence level?

-Thus it is not clear if the 979 subjects who performed the on-line survey were all recovered for COVID-19.

-The group analyzed is manily composed from young adults sice only 2.7% were >50 years. Thus results obtained aremailny reppresentative of the post recovery in young adults patients.

-No statistical analysis is present. Only mean and frequency.

-Again, authors should also mentioned that on-line survey can be affected from the subjective perception of the interviewed.

-Elderlies are highly affected with harmful post recovery long-term symptoms, but this group is missing

-In tables included in the manuscript, when authors mention: "mean" and "frequency" please include also to what they are refering for, as days.

**********

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Reviewer #1: No

Reviewer #2: No

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30 May 2021

Department of Medical Biochemistry,

College of Medicine,

Qassim University,

Buraidah, KSA.

May 28, 2021

Tauqeer Hussain Mallhi, Ph.D

Academic Editor

PLOS ONE

Dear Professor Mallhi:

Thank you for giving us the opportunity to revise our manuscript # PONE-D-21-02645, entitled “COVID-19: Post recovery long-term symptoms among patients in Saudi Arabia”. The manuscript has been revised in light of the reviewers’ comments for publication in PLOS ONE. The material contained in the manuscript is original and has not been submitted for publication elsewhere.

We have addressed all the concerns raised by reviewers as detailed under the enclosed point-by-point reply to the reviewers.

We continue to express our gratitude to the reviewer’s constructive criticisms, which have improved the quality of the manuscript. We hope that the reviewers will find the answers satisfactory.

Sincerely,

Corresponding Author

Zafar Rasheed, MS., PhD., PGDCA.

ORCID ID: http://orcid.org/0000-0002-8651-4218

Email: zafarrasheed@qumed.edu.sa

Point-by-Point Response to the Reviewers’ Comments

Manuscript Number: PONE-D-21-02645

Manuscript title: COVID-19: Post recovery long-term symptoms among patients in Saudi Arabia

Journal: PLOS ONE

We are grateful to the reviewers for their thorough reviews and for constructive comments, which enabled us to further improve our manuscript. Concerns raised have been addressed below.

Please note that all the changes in the revised manuscript are highlighted.

REVIEWERS REPORTS:

Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Author’s Response:

We highly appreciate to the reviewers and the editors for their thorough reviews. The manuscript has been revised exactly in the same ways as per of your suggestions. Please note that all changes in the revised manuscript are highlighted.

Reviewer 1: Report

In their paper COVID-19: Post recovery long-term symptoms among patients in Saudi Arabia, Khodeir et al aimed to identify long-term symptoms in different body systems symptoms following COVID-19, their severity, and their duration as a first step in building a system to classify post-recovery long-term symptoms of coronavirus disease 2019 (COVID-19). They conclude that Long-term symptoms after recovery from COVID-19 warrant patient follow-up. The authors propose a classification system as a starting point to guide the identification and follow-up of long-term symptoms post-recovery, and recommend larger-scale studies to broaden the definition of recovery from COVID-19, which appears to have two phases, acute and chronic. While the goal of this paper is interesting, several improvements can be made to this paper.

Author’s Response:

We highly appreciate for your excellent review, which definitely helped us to further improve the quality of the manuscript. All suggestions have now been incorporated in the revised manuscript.

Specific Comments

Comment # 1:

The methods section requires expansion, a copy of the questionnaire, its translation etc. needs to be placed in the methods.

Author’s Response:

We highly appreciate you for your thorough review. As suggested, the used questionnaire and its translation have now been included in the methods subsection ‘Instrument development and measures’ on page 5 and 6 and the complete details of used questionnaire with translation have now been added in table 1 of the revised manuscript on page 7 and 8.

Comment # 2.

The statistics portion requires more sophisticated analysis. For example, usually the mean is reported with SD, and the median is reported with the interquartile range and/or range. Here the authors report the mean SD and range. Also, to develop a score or classification system, there has to be an end point. For example, what is the goal of this classification? Is there a stage? Is there a score? Is one type better than the others. Several adjustments of baseline characteristics are needed. Saudi versus non-Saudi is not needed, Race, ethnicity, work, etc. may be better. LOTS of improvement may be made to this section.

Author’s Response:

We highly appreciate for your excellent review and for pointing out these. As suggested, a detailed statistical analysis have now been performed and included in the methods section, results section and also in the discussion sections. Specifically, we have now been added more detailed scoring system with different levels of priorities for patient follow up and cut off values. Please see the newly statistical data in the revised Table 3, 4, 5 and 6 on page 12,13,19-21, respectively and also see the newly added figure 1 and 2. Furthermore, the data on nationality of the studied subject have now been omitted as suggested. Please note table numbers in the revised manuscript are changed.

Comment # 3.

The results section needs more details. I think reporting the “classification system” reposting a “scale for it” briefly reporting the populations. Again, improvements need to be made

Author’s Response:

Thanks for your useful suggestion which definitely helped us to further improve the quality of the manuscript. As suggested, more details in the results section have now been included in the revised manuscript. Please see the highlighted text in Tables 2-4 on page 11-13 and also see the added data in figures 1-3. Furthermore, please also see the highlighted text in the results section on page 17, line 3-23 and page 18, line 1-4.

Comment # 4.

The tables could become one table

Author’s Response:

Thanks. All possible modifications in the tabular presentation have been made in the revised manuscript. In addition, the data have also now been presented in the forms of figures. Please note table numbers in the revised manuscript are changed.

Comment # 5.

Figures would help deliver the message better

Author’s Response:

Thanks. As suggested, figures have now been included in the revised manuscript. Please see the data in newly data figures 1-3.

Comment # 6.

The conclusion is too long, and should not have references or references to tables, this should move to the discussion. The conclusion summarizes your findings, not others.

Author’s Response:

As suggested, the conclusion section has now been revised and the word count has now been significantly reduced. All text with citations has been shifted and discussed in the discussion section. Please see the highlighted text on page 17, line 3-23, page 18, line 1-4 in the discussion section and also page 21, line 10-20 in the conclusion section of the revised manuscript.

Comment # 7.

In summary, while the findings and goal of the study is quite good, the structure of this paper could improve.

Author’s Response:

We highly appreciate your for your constructive criticisms and positive comments, which definitely have improved the quality of the manuscript.

Reviewer 2: Report

In the manuscript authored by Mostafa Khodeir et al, the authors reported results obtained from an on-line survey about the post recovery long-term symptoms among patients in Saudi Arabia. Despite manuscript is valuable in the attempt here below I reported my comments and suggestions.

Author’s Response:

We are grateful to you for your thorough review and for your constructive comments. All concerns raised have been addressed below. Please note that all major changes in the revised manuscript are highlighted.

Comment # 1:

It is not clear in the method section how subjects have been included. Authors stated: "The estimated sample size was 663, which was obtained by statistical calculation from the official Saudi Ministry of Health website, which announced the number of recovered cases with a 99% confidence level and a 5% margin of error". Thus, why authors did not contacted directly those 663 persons? It is correct the 99% confidence level?

Author’s Response:

Thanks for your thorough review and pointing out these. As suggested, more details in the methods section have now been provided to clarify how the participants were included. Now we have changed the confidence level to 95% and the details of recalculation of the sample size have been provided on page 9, line 1-4 in the revised manuscript. We are also pleased to inform that our survey response exceeded the calculated sample size in both situations of CI 95% or 99%. We would also like to inform that we had not contacted the cases directly in person because of some obstacles such as (a) social and precautionary measures and restrictions in the country, (b) fear of recovered persons to contact hospital or clinics for reinfection (still deficient information about the disease), (c) difficulties in transportation and feasibility time of the respondents, (d) there is still no clear concept about the need of recovered COVID-19 cases for follow up, therefore we considered the piloted sample (40 cases) to continue the study by online survey not to bother the respondents and also the urgency to know more about the disease to recommend all required measures to manage COVID-19 especially those missed and considered recovered by just recovery from acute symptoms. Now we have clearly mentioned that the survey was conducted online and the limitations of the study have also been clearly defined in the revised methods section on page 6, line 15-22.

Comment # 2:

Thus it is not clear if the 979 subjects who performed the on-line survey were all recovered for COVID-19.

Author’s Response:

Yes. All were recovered from acute symptoms of COVID-19. We have now added this information in the results section on page 9, line 17 and 18 of the revised manuscript.

Comment # 3:

The group analyzed is mainly composed from young adults since only 2.7% were >50 years. Thus results obtained are mainly representative of the post recovery in young adults patients.

Author’s Response:

Yes, this information is 100% correct. This could be explained as the survey being done online which is easier for young. This important information has now been added in the limitations of the study of the revised manuscript.

Comment # 4:

No statistical analysis is present. Only mean and frequency.

Authors Response:

As suggested, more statistical analysis details have now been included throughout the manuscript including tables and figures. And the details of the used statistical methods have been summarized in the revised manuscript on page 9, line 6-14.

Comment # 5:

Again, authors should also mentioned that on-line survey can be affected from the subjective perception of the interviewed.

Author’s Response:

We highly appreciate for your thorough review and pointing out this. As suggested, this detail has now been included in the limitations of the study on page 16&17, and also in the limitation of questionnaire on page 6 of the revised manuscript.

Comment # 6:

Elderlies are highly affected with harmful post recovery long-term symptoms, but this group is missing.

Author’s Response:

Thanks for your suggestion and pointing out this. As suggested, the detail of this missing age group has now been included. Now we performed analysis on the basis of age group distribution where elderlies were characterized as 60 or above years of age. These details are summarized in Table 2 of the revised manuscript on page 11.

Comment # 7:

In tables included in the manuscript, when authors mention: "mean" and "frequency" please include also to what they are refering for, as days.

Author’s Response:

Thanks. As suggested, the tables have now been revised and the suggested details of referring of days have now been included in the revised tables 3 and 5 on page 12&13 and their related text has now been added and highlighted in the results section on page 9 and 10 and discussed in the discussion section on page 12-13 in the revised manuscript.

________________________________________

Reviewer's Responses to the Editorial Questions: Author’s Response

Comment # 1: Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Partly

Author’s Response:

We highly appreciate both of the reviewers for their thorough review and constructive criticisms, which helped us to further improved the quality of the manuscript. We have addressed all the concerns raised above and hope that the both of you find the answers satisfactory.

Comment # 2: Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: No

Author’s Response:

Thanks. This part has also been significantly improved by addition of more statistical analyzed data. Please see the highlighted text in the methods section, results section and particularly tables and figures of the revised manuscript.

Comment # 3: Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Author’s Response:

We highly appreciate for the positive comments.

Comment # 4: Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: Yes

Author’s Response:

Thanks. As suggested by the editorial members, the manuscript has been edited by an expert English Editing Company (Editage) and also has now been revised by one of our English language experts. Now we hope that the revised manuscript will now meet the high standards of the journal and suitable for publication in PLOS ONE.

________________________________________

EDITORIAL COMMENTS

Comment # 1:

Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf

and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Author’s Response:

We highly appreciate the editorial board of PLOS ONE for giving us an opportunity to revise our manuscript. The manuscript has now been revised exactly in the same format as instructed.

Comment # 2:

Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information.

Author’s Response:

Thanks. Informed consent statement has now been well defined and included in the methods section on page 4, line 24; page 5, lines 1 and line 5-8 in the revised manuscript. Please note all changes made in the revised manuscript are highlighted.

Comment # 3:

Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information. Moreover, please include more details on how the questionnaire was pre-tested, and whether it was validated.

Author’s Response:

As suggested by you and one of the reviewers, the complete details of the questionnaire have now been included and its copy with Arabic translation has been inserted in the methods section on page 7 and 8. Furthermore, all possible details of the questionnaire including its validation have now been added in the methods subsection ‘Instrument development and measures’ on page 5 and 6 of the revised manuscript.

Comment # 4:

Thank you for stating the following financial disclosure: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." At this time, please address the following queries:

Comment # 4 (a): Please clarify the sources of funding (financial or material support) for your study. List the grants or organizations that supported your study, including funding received from your institution.

Author’s Response:

We as authors hereby declared that this study has no association with any of the funding agencies.

Comment # 4 (b): State what role the funders took in the study. If the funders had no role in your study, please state: “The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”

Author’s Response:

We declared that “The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript”. This statement has also now been mentioned in the ‘Funding support’ section of the revised manuscript on page 22, line 14-16.

Comment # 4 (c): If any authors received a salary from any of your funders, please state which authors and which funders.

Author’s Response:

None.

Comment # 4 (d): If you did not receive any funding for this study, please state: “The authors received no specific funding for this work.” Please include your amended statements within your cover letter; we will change the online submission form on your behalf

Authors Response:

Thanks. We hereby declared that “The authors received no specific funding for this work.”

Comment # 5:

Please include your tables as part of your main manuscript and remove the individual files. Please note that supplementary tables (should remain/ be uploaded) as separate "supporting information" files

Authors Response:

Thanks. As suggested, all tables have now been inserted in the main manuscript.

Comment # 6:

Additional Editor Comments (if provided):

Dear Authors, thank you for submitting in Plos One. Your manuscript has been assessed by relevant experts from the field. They found manuscript interesting but raised some concerns in methodology (study instrument validation and translation, sampling technique and methods of recruitment) and interpretation of results. It is requested to please consider the comments of reviewers.

Author’s Response:

Thank you for giving us the opportunity to revise this manuscript. The manuscript has been revised in light of the reviewers’ and editorial comments for publication and we believe that the revised manuscript will now meet the high standards of the journal and suitable for publication in “PLOS ONE”.

Corresponding Author

Zafar Rasheed, MS, PhD, PGDCA.

ORCID ID: http://orcid.org/0000-0002-8651-4218

Submitted filename: Response to the Reviewers.docx

Click here for additional data file.

28 Jul 2021

PONE-D-21-02645R1

COVID-19: Post recovery long-term symptoms among patients in Saudi Arabia

PLOS ONE

Dear Dr. Rasheed,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Sep 11 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Tauqeer Hussain Mallhi, Ph.D

Academic Editor

PLOS ONE

Journal Requirements:

Additional Editor Comments (if provided):

Dear Authors, thank you for revising the manuscript. Your manuscript has been again assessed by relevant experts. They found manuscript interesting but raised few more concerns in methodology (pilot study, sampling methods etc) and interpretation of results. It is requested to please consider the comments of reviewers.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

Reviewer #4: (No Response)

Reviewer #5: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: Partly

Reviewer #4: Yes

Reviewer #5: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: No

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: No

Reviewer #4: Yes

Reviewer #5: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: Authors provided most of the suggestions and modification requested. Now the manuscript has been improved, thus I suggest it for a pubblication in PLOSone

Reviewer #3: Appreciating the authors for their response to the required comments. However, the manuscript still needs English language editing.

Reviewer #4: COVID-19: Post recovery long-term symptoms among 2 patients in Saudi Arabia

Review

Shorten the paper to around 6000 words.

Questionnaire need not be shown in the manuscript

Rewrite the manuscript with all results in one section.

Reviewer #5: With this ongoing World War against this COVID-19 thing, this manuscript addresses a hot topic in which any effort in this concern is highly appreciated. The study is generally scientifically sound however; some important points need to be clarified. These include (on the revised version of the submission):

1) Page 5, lines 1-2: The authors wrote: "A survey was administered between September and October 2020 using Google Forms and Twitter as a forum".

Well, the conclusions based on the answers extracted from a survey on the social media platform are usually taken with extreme caution. So, this point has to be CLEARLY mentioned in the Limitation(s) Section.

2) Page 6, lines 1-2: The authors wrote "The results of the pilot study were not included in any subsequent research". OK, the result of validity and reliability test of the questionnaire has to be included.

3) Page9, line1: OK, here the readers are definitely going to get confused about how the author managed to get this particular figure (384) as a sample size beside, line 17 on the same page 9 tells a completely different story about the number of subjects recruited (979) with no clue whatsoever. So the authors need to mention the whole story of the sample size calculation.

4) Page 16; Line 23: The authors wrote: “This study has few limitations such as”.

OK here is the thing; I encourage the authors to avoid this kind of open statements which include “such as and/or etc.” So, I do urge the authors to precisely count down all these limitations. Speaking of limitation, I suggest gathering all these limitations under one separate section (subtitle).

5) Tables 4 to 6B: (N) is to be mentioned.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #3: Yes: Walid Kamal Abdelbasset

Reviewer #4: Yes: Asharaf Abdul Salam

Reviewer #5: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

3 Aug 2021

Point-by-Point Re-Response to the Reviewers’ Comments

Manuscript Number: PONE-D-21-02645R1

Manuscript title: COVID-19: Post recovery long-term symptoms among patients in Saudi Arabia

Journal: PLOS ONE

We are grateful to the reviewers and editors for their thorough reviews and for constructive comments, which enabled us to further re-improve our manuscript. Concerns raised have been re-addressed below.

Please note that all major changes in the Re-revised manuscript are highlighted.

REVIEWERS' COMMENTS:

Reviewer's Responses to Questions

Comments to the Author

---------------------------------------------------------------------------------------------------------------------

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer # 2: All comments have been addressed

Author’s Response: We highly appreciate your positive feedback.

Reviewer # 3: All comments have been addressed

Author’s Response: We highly appreciate your positive feedback.

Reviewer # 4: (No Response)

Author’s Response: We highly appreciate your thorough review, which helped us to further improve the quality of the manuscript.

Reviewer # 5: (No Response)

Author’s Response: We highly appreciate your thorough review, which helped us to further improve the quality of the manuscript.

---------------------------------------------------------------------------------------------------------------------

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer # 2: Yes

Author’s Response: We highly appreciate your positive feedback.

Reviewer # 3: Partly

Author’s Response: We highly appreciate for the positive response. The manuscript has now been re-revised in light of your comments.

Reviewer # 4: Yes

Author’s Response: We highly appreciate your positive feedback.

Reviewer # 5: Partly

Author’s Response: We highly appreciate your positive feedback. The manuscript has now been re-revised in light of your comments.

---------------------------------------------------------------------------------------------------------------------

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer # 2: Yes

Author’s Response: We highly appreciate your positive feedback.

Reviewer # 3: Yes

Author’s Response: We highly appreciate your positive feedback.

Reviewer # 4: Yes

Author’s Response: We highly appreciate your positive response.

Reviewer # 5: Yes

Author’s Response: We highly appreciate your positive response.

---------------------------------------------------------------------------------------------------------------------

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer # 2: Yes

Author’s Response: We highly appreciate your positive feedback.

Reviewer # 3: Yes

Author’s Response: We highly appreciate your positive feedback.

Reviewer # 4: Yes

Author’s Response: We highly appreciate your positive feedback.

Reviewer # 5: No

Author’s Response: We highly appreciate your thorough reviews. The manuscript has now been re-revised as per of your suggestions.

---------------------------------------------------------------------------------------------------------------------

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer # 2: Yes

Author’s Response: We highly appreciate your positive feedback.

Reviewer # 3: No

Author’s Response: We highly appreciate your thorough reviews. The manuscript has now been re-revised as per of your suggestions.

Reviewer # 4: Yes

Author’s Response: We highly appreciate your positive feedback.

Reviewer # 5: Yes

Author’s Response: We highly appreciate your positive feedback.

---------------------------------------------------------------------------------------------------------------------

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer # 2: Authors provided most of the suggestions and modification requested. Now the manuscript has been improved, thus I suggest it for a publication in PLOSone

Author’s Response: Many thanks for your positive response.

Reviewer # 3: Appreciating the authors for their response to the required comments. However, the manuscript still needs English language editing.

Author’s Response: We highly appreciate your positive feedback. This manuscript has been edited by an expert English Editing Company Editage and also has now been Re-revised by one of our English language experts.

Reviewer # 4: COVID-19: Post recovery long-term symptoms among 2 patients in Saudi Arabia.

Review report:

(a) Shorten the paper to around 6000 words.

Author’s Response: As suggested, the manuscript has now been reduced to ~5500 words.

(b) Questionnaire need not be shown in the manuscript.

Author’s Response: As suggested, the questionnaire has now been omitted from the re-revised manuscript. Respectfully, we would like to inform that we have placed the questionnaire in the previous version of this manuscript as per instructions of reviewer # 1, which has now been presented as a supplementary file.

(c) Rewrite the manuscript with all results in one section.

Author’s Response: Thanks. All results have now been presented in one section.

Reviewer # 5: With this ongoing World War against this COVID-19 thing, this manuscript addresses a hot topic in which any effort in this concern is highly appreciated. The study is generally scientifically sound however; some important points need to be clarified. These include (on the revised version of the submission):

1) Page 5, lines 1-2: The authors wrote: "A survey was administered between September and October 2020 using Google Forms and Twitter as a forum". Well, the conclusions based on the answers extracted from a survey on the social media platform are usually taken with extreme caution. So, this point has to be CLEARLY mentioned in the Limitation(s) Section.

Author’s Response: We highly appreciate your positive feedback. As suggested, the limitation section has now been modified by taking caution. The ways of questionnaire administration have now been well discussed in the limitations of the study on page 18, line 12-21 in the re-revised manuscript.

2) Page 6, lines 1-2: The authors wrote "The results of the pilot study were not included in any subsequent research". OK, the result of validity and reliability test of the questionnaire has to be included.

Author’s Response: Excellent suggestion. As suggested, the validity and reliability test of the questionnaire have now been included in the revised manuscript on page 6, line 1-9 and their associated references have also been cited. Please see the newly added references # 36 and 37 in the reference list on page 24.

3) Page 9, line 1: OK, here the readers are definitely going to get confused about how the author managed to get this particular figure (384) as a sample size beside, line 17 on the same page 9 tells a completely different story about the number of subjects recruited (979) with no clue whatsoever. So the authors need to mention the whole story of the sample size calculation.

Author’s Response: Thanks for your excellent suggestion. As suggested, this useful information of sample size has now been added in the revised manuscript on page 7, line 4-9.

4) Page 16; Line 23: The authors wrote: “This study has few limitations such as”.

OK here is the thing; I encourage the authors to avoid this kind of open statements which include “such as and/or etc.” So, I do urge the authors to precisely count down all these limitations. Speaking of limitation, I suggest gathering all these limitations under one separate section (subtitle).

Author’s Response: Thanks. As suggested, all limitations have now been gathered and discussed in the last part of the discussion section on page 18, line 12-21 in the revised manuscript.

5) Tables 4 to 6B: (N) is to be mentioned.

Author’s Response: Thanks. All tables and figures have now been cited in the results section of the re-revised manuscript.

---------------------------------------------------------------------------------------------------------------------

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #3: Yes: Walid Kamal Abdelbasset

Reviewer #4: Yes: Asharaf Abdul Salam

Reviewer #5: No

Author’s Response: We highly appreciate all the reviewers for their excellent review, which have improved the quality of the manuscript.

We believe that the Re-revised manuscript will now meet the high standards of the journal and suitable for publication in “PLOS ONE”.

Corresponding Author

Zafar Rasheed, MS, PhD, PGDCA.

ORCID ID: http://orcid.org/0000-0002-8651-4218

Submitted filename: Re-Response to the Reviewers.docx

Click here for additional data file.

13 Sep 2021

PONE-D-21-02645R2COVID-19: Post recovery long-term symptoms among patients in Saudi ArabiaPLOS ONE

Dear Dr. Rasheed,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Oct 28 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

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We look forward to receiving your revised manuscript.

Kind regards,

Tauqeer Hussain Mallhi, Ph.D

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments (if provided):

Dear Authors, thank you for revising the draft. This manuscript has improved substantially. However, referee raised few concerns over the limitation of the project. Please address the comments and submit the draft at your earliest.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

Reviewer #4: All comments have been addressed

Reviewer #5: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: N/A

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: No

Reviewer #5: No

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: (No Response)

Reviewer #3: All required comments have been addressed. The manuscript is presented in an intelligible fashion and written in standard English?I have no further comments. Congrats.

Reviewer #4: COVID-19: Post recovery long-term symptoms among patients in Saudi Arabia

1. A total of 979 patients 10 recovered from COVID-19 in Saudi Arabia in the study period, of whom 53% were male and 47% were female.

Sample size is appreciated as such studies from Saudi Arabia are rare, but not this male-female proportions. It is stated that males are affected more than females. Here the difference is not large.

3–5 min (P5; L8) may change to 3-5 minutes

Instrument development and measures section is one paragraph. Consider splitting into two or even three.

Final questionnaire was structured into 6 sections 10 addressing specific symptoms (P6 L 9-10) – In case the authors adopted any classification system, the same may be referred.

In P7 the following statements need explanations a. a total of 992 subjects were approached b. 13 subjects were omitted as they were made invalid selection and c. 979 subjects were recruited. Whether used a sample frame or a followed a list of subjects. Sample representativeness needs to be explained.

Of the 979 respondents’ patients (P8)- use of ‘

respectively) (Table 3) (P8; L18)– Avoid two parentheses together

Furthermore, we also found 21 a statistically significant relation of age with the presence of post-recovery COVID-19 long term 22 symptoms degree of severity and/or persistence, such as weakness degree (p= 0.003), persistence (p=0.001), lack of appetite degree (p=0.02), persistence (p=0.003), Insomnia degree (p=0.01), 9 1 loss of smell degree (p=0.002), loss of taste degree and Headache degree (p=0.04 each), cough 2 degree (p=0.01) significant correlation was found between age and persistence of symptoms as 3 fatigue (p=0.004), joint pains (p=0.01), mood changes (p=0.03), nausea (p=0.002) and 4 abdominal pain (p=0.02)( Table 2&3) – Please check the tables and clear confusions by including age in the table titles and columns.

The proposed scoring system in this study can be delivered online for post discharge follow-up, and the score of each case can be automatically calculated. The case that will reach the proposed score should be invited for follow up in the clinic, keeping in mind high concerns groups (Table 4 level 1A&B) are first priority follow up group, while lower concerns groups (Table 5 level 2 A&B) are of second priority follow up. The cases not reached the proposed score no need for clinic follow up and should be reassured as mostly their symptoms be self-limited. By this scoring system we can easily pickup patients of concern to be followed up and also decrease load on health services as much as possible. Why these lines stand different????

Table 2 shows a wide range days (upto 120 days). It would be nice to explain column by column. You may use either mean days or median days. It is nice to state the statistical test performed for reaching out the p value.

Results need to be further elaborated for readers to understand.

Use smaller paragraphs in discussions. I mean, break ideas into paragraphs.

we can’t expect who will suffer (P17, L 9) may be reworded

Our scoring system will help to broaden the view of the scoring system that used to classify the acute cases of COVID-19 into mild, moderate, severe, or critical which proposed by The Chinese National Health Commission [64]. We aimed by our scoring system to map and score, as an initial step to build a scoring system, the recorded long-term symptoms to avoid missing such cases who may suffer a sequalae later on, keeping in mind the exact pathogenesis is still unclear. Our proposed scoring system can be delivered online for post discharge follow-up, and can be automatically calculated the score of each case. The case that will reach the proposed score (score 2) should invited for follow up in the clinic, keeping in mind high concerns groups are first priority follow up group, while lower concerns groups are of second priority follow up. The cases not reached the proposed score no need for clinic follow up and should be reassured as mostly their symptoms be self-limited. By this scoring system we can easily pickup patients of concern to be followed up and also decrease load on health services as much as possible. Again, this scoring system could be applied online weekly and so we can get a wider scale and broader view on behavior of these long-term symptoms. Our proposed scoring system and categorization of patients into high concern and lower concern groups may considered as an initial step that help and encourage a wider scale studies in different countries to confirm and refine the findings by considering geographical distribution and a larger number of COVID-19 cases. This will help to identify priorities in follow-up among patients according to longer-term symptoms and to avoid prolonged suffering in those who recover from COVID-19. (P17-18). Do not match with the discussions, that is wrongly placed.

Acknowledgments The authors thank all health services personnel and volunteers who are on the front lines of the pandemic and have expended great effort to fight the disease all over the world. Special thanks to those who sacrificed their lives to save thousands of others. The authors also thank those who devoted their time and exerted extraordinary effort to create vaccines to ease—if not eliminate— 22 suffering around the world. Authors may acknowledge those who helped them in this research and manuscript preparation.

Reviewer #5: Because they are too many and significantly affect the reliability of all the conclusions and recommendations drawn, all limitations are to be gathered in a separate section under the subtitle "LIMITATIONS" and NOT as a paragraph in the "Discussion" section.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #3: Yes: Walid Kamal Abdelbasset

Reviewer #4: Yes: Asharaf Abdul Salam

Reviewer #5: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

8 Oct 2021

Point-by-Point Re-Response to the Reviewers’ Comments

Manuscript Number: PONE-D-21-02645R2

Manuscript title: COVID-19: Post recovery long-term symptoms among patients in Saudi Arabia

Journal: PLOS ONE

We are grateful to all the reviewers for their thorough reviews and for constructive comments, which enabled us to further re-improve our manuscript. Concerns raised have been re-addressed below.

Please note that all major changes in the Re-revised manuscript are highlighted.

REVIEWERS' COMMENTS:

Reviewer # 1: Final Report Outcome

Author’s Response: We highly appreciate you for the positive feedback

Reviewer # 2: Final Report Outcome

Author’s Response: We highly appreciate you for the positive feedback

Reviewer # 3: Final Report Outcome

Author’s Response: We highly appreciate you for the positive feedback

Reviewer # 4: Report

COVID-19: Post recovery long-term symptoms among patients in Saudi Arabia

Comment 1:

A total of 979 patients 10 recovered from COVID-19 in Saudi Arabia in the study period, of whom 53% were male and 47% were female. Sample size is appreciated as such studies from Saudi Arabia are rare, but not this male-female proportions. It is stated that males are affected more than females. Here the difference is not large.

Author’s Response:

It has now been corrected on page 8, line 3 in the re-revised manuscript.

Comment 2:

3–5 min (P5; L8) may change to 3-5 minutes

Author’s Response:

As suggested, it has now been changed.

Comment 3: Instrument development and measures section is one paragraph. Consider splitting into two or even three.

Author’s Response:

As suggested, this paragraph has now been splitted into two subsections on page 5 and 6 in the re-revised manuscript.

Comment 4: Final questionnaire was structured into 6 sections 10 addressing specific symptoms (P6 L 9-10) – In case the authors adopted any classification system, the same may be referred.

Author’s Response:

We mentioned that ‘the questionnaire used in this study was created using a combination of published literature and the literature used was well cited on page 5, line 14 and 15.

Comment 5: In P7 the following statements need explanations a. a total of 992 subjects were approached b. 13 subjects were omitted as they were made invalid selection and c. 979 subjects were recruited. Whether used a sample frame or a followed a list of subjects. Sample representativeness needs to be explained.

Author’s Response:

Thanks. Sample representativeness has now been mentioned and highlighted on page 7, line 8 in the re-revised manuscript. All subjects were Saudi citizens.

Comment 6: Of the 979 respondents’ patients (P8)- use of ‘

Author’s Response: It has now been corrected on page 8, line 2.

Comment 7: respectively) (Table 3) (P8; L18) – Avoid two parentheses together

Author’s Response: Thanks, this has also now corrected.

Comment 8: Furthermore, we also found 21 a statistically significant relation of age with the presence of post-recovery COVID-19 long term 22 symptoms degree of severity and/or persistence, such as weakness degree (p= 0.003), persistence (p=0.001), lack of appetite degree (p=0.02), persistence (p=0.003), Insomnia degree (p=0.01), 9 1 loss of smell degree (p=0.002), loss of taste degree and Headache degree (p=0.04 each), cough 2 degree (p=0.01) significant correlation was found between age and persistence of symptoms as 3 fatigue (p=0.004), joint pains (p=0.01), mood changes (p=0.03), nausea (p=0.002) and 4 abdominal pain (p=0.02)( Table 2&3) – Please check the tables and clear confusions by including age in the table titles and columns.

Author’s Response:

We have now re-checked both of these tables and the mean (±SD) age of the studied subjects in years has now been added in their titles in the re-revised manuscript as per of your suggestions.

Comment 9: The proposed scoring system in this study can be delivered online for post discharge follow-up, and the score of each case can be automatically calculated. The case that will reach the proposed score should be invited for follow up in the clinic, keeping in mind high concerns groups (Table 4 level 1A&B) are first priority follow up group, while lower concerns groups (Table 5 level 2 A&B) are of second priority follow up. The cases not reached the proposed score no need for clinic follow up and should be reassured as mostly their symptoms be self-limited. By this scoring system we can easily pickup patients of concern to be followed up and also decrease load on health services as much as possible. Why these lines stand different????

Author’s Response:

This paragraph is linked to our findings. For more clarity to the readers to understand, we have made some modifications in this paragraph on page 7, line 5-15 in the re-revised manuscript.

Comment 10: Table 2 shows a wide range days (upto 120 days). It would be nice to explain column by column. You may use either mean days or median days. It is nice to state the statistical test performed for reaching out the p value. Results need to be further elaborated for readers to understand. Use smaller paragraphs in discussions. I mean, break ideas into paragraphs.

Author’s Response:

Thanks. The data in mean days as well as median days have already mentioned in the Table 2. As suggested, the statistical test used to measure p values has now been added in the table legend. Moreover, the discussion sections has now been divided into smaller paragraphs. Please note only major changes in the re-revised manuscript are highlighted.

Comment 11: we can’t expect who will suffer (P17, L 9) may be reworded. Our scoring system will help to broaden the view of the scoring system that used to classify the acute cases of COVID-19 into mild, moderate, severe, or critical which proposed by The Chinese National Health Commission [64]. We aimed by our scoring system to map and score, as an initial step to build a scoring system, the recorded long-term symptoms to avoid missing such cases who may suffer a sequalae later on, keeping in mind the exact pathogenesis is still unclear. Our proposed scoring system can be delivered online for post discharge follow-up, and can be automatically calculated the score of each case. The case that will reach the proposed score (score 2) should invited for follow up in the clinic, keeping in mind high concerns groups are first priority follow up group, while lower concerns groups are of second priority follow up. The cases not reached the proposed score no need for clinic follow up and should be reassured as mostly their symptoms be self-limited. By this scoring system we can easily pickup patients of concern to be followed up and also decrease load on health services as much as possible. Again, this scoring system could be applied online weekly and so we can get a wider scale and broader view on behavior of these long-term symptoms. Our proposed scoring system and categorization of patients into high concern and lower concern groups may considered as an initial step that help and encourage a wider scale studies in different countries to confirm and refine the findings by considering geographical distribution and a larger number of COVID-19 cases. This will help to identify priorities in follow-up among patients according to longer-term symptoms and to avoid prolonged suffering in those who recover from COVID-19. (P17-18). Do not match with the discussions, that is wrongly placed.

Author’s Response:

Thanks. This paragraph has now been omitted from the discussion section of the re-revised manuscript.

Comment 12: Acknowledgments: The authors thank all health services personnel and volunteers who are on the front lines of the pandemic and have expended great effort to fight the disease all over the world. Special thanks to those who sacrificed their lives to save thousands of others. The authors also thank those who devoted their time and exerted extraordinary effort to create vaccines to ease—if not eliminate— 22 suffering around the world. Authors may acknowledge those who helped them in this research and manuscript preparation.

Author’s Response:

The paragraph you copied from the acknowledgement section and pasted above has already mentioned the acknowledgments of all the services, personnel and volunteers that we utilized in the preparation of this manuscript. Respectfully, we are very pleased to inform that all authors themselves participated in this research and in the preparation of manuscript.

Reviewer # 5: Report

Because they are too many and significantly affect the reliability of all the conclusions and recommendations drawn, all limitations are to be gathered in a separate section under the subtitle "LIMITATIONS" and NOT as a paragraph in the "Discussion" section.

Author’s Response:

Thanks for your review and for the suggestions. As suggested, study limitations have now been presented in a separate section.

We believe that this revised manuscript will now meet the high standards of the journal and suitable for publication in “PLOS ONE”.

Corresponding Author

Zafar Rasheed, MS, PhD, PGDCA.

ORCID ID: http://orcid.org/0000-0002-8651-4218

Submitted filename: Response to the Reviewers Oct 8, 2021.docx

Click here for additional data file.

8 Nov 2021

COVID-19: Post recovery long-term symptoms among patients in Saudi Arabia

PONE-D-21-02645R3

Dear Dr. Rasheed,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

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Kind regards,

Tauqeer Hussain Mallhi, Ph.D

Academic Editor

PLOS ONE

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Reviewers' comments:

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Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

Reviewer #5: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #5: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #5: (No Response)

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4. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #5: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #5: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: Authors provided most of the corrections requested from the reviewers and now the manuscript has been highly improved.

Reviewer #3: Appreciating the authors for their complete responses to all comments required by the reviewers. I have no additional comments.

Reviewer #5: (No Response)

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Reviewer #2: No

Reviewer #3: Yes: Walid Kamal Abdelbasset

Reviewer #5: No

15 Nov 2021

PONE-D-21-02645R3

COVID-19: Post recovery long-term symptoms among patients in Saudi Arabia

Dear Dr. Rasheed:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Tauqeer Hussain Mallhi

Academic Editor

PLOS ONE