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. 2022 Apr 25;17(9):673–682. doi: 10.2217/fmb-2022-0041

Recurrent viral RNA positivity and candidiasis findings in hospitalized patients with COVID-19

Malihe Naderi 1,2, Seyed Amir Soltani 3, Akram Taheri Rad 4, Zahra Mehrbakhsh 5,6, Sina Sodagar 7, Alireza Tahamtan 1, Seyedeh Sedigheh Hosseini 7,8,*
PMCID: PMC9248024  PMID: 35465729

Abstract

Background: The aim of this study was to evaluate reinfection and fungal infections among 785 patients with COVID-19 disease admitted to Baqiyatallah Hospital in Northeastern Iran after the onset of the COVID-19 epidemic. Materials & Methods: In this descriptive-analytic study (20 February–21 July 2020), reinfection and fungal infections among 785 patients were investigated using epidemiological questionnaire, clinical trials, Real-time PCR and CT scan (chest computed tomography) from the hospital HIS (hospital's information system) and collected samples. Results: Reinfection and one oral candidiasis were diagnosed in one 68-year-old man and one 47-year-old man 63 and 42 days after the initial infection, respectively. Conclusion: The research results showed that exposure to COVID-19 may not establish long-term protective immunity to all patients.

Keywords: : candidiasis, COVID-19, real-time PCR, reinfection

COVID-19, caused by coronavirus, has turned into a worldwide epidemic [1] and become an ‘international public health emergency’ [2]. Therefore, diagnosis is essential to provide better services to the patients suffering from this disease and prevent further transmission of it [3]. Despite the passage of time from the COVID-19 pandemic, development of various symptoms, and involvement of different organs of the human body, there are still various questions about the course of the disease and reinfection [4]. In some patients, discontinuation of the drug after recovery from clinical symptoms may lead to the recurrence of the disease rarely may due to SARS-CoV-2 long-term shedding and increased virus replication [5]. Reinfection in recovered patients is a serious problem that is considered as a secondary source of virus spread. On the other hand, reinfection may occur in different forms that are diagnosed in clinical and laboratory samples in respiratory syndrome [6]. Many studies have reported the interval between the first infection and reinfection as 20–22 days for complete removal of COVID-19 from the patient's body, but due to differences in age and gender, for establishing immune responses, is not possible to report it accurately [4].

COVID-19 patients have clinical symptoms like respiratory failure due to lung involvement as the first target organ [7] and dysfunction of several other organs [8]. It is worth noting that the patient may experience severe symptoms such as fever, cough, lymphopenia, etc, that may occur in some of them simultaneously [9–13]. Clinical data suggest that risk factors include old age and some diseases such as cardiovascular diseases (CVDs), diabetes, chronic respiratory disease, malignancy and other diseases that can exacerbate this viral infection or increase the rate of death [14–17] by predisposing a person to coronavirus infection due to persistent inflammation and impaired immune response [18–20].

Owing to the simultaneous administration of several antibiotics in patients with COVID-19, oral diseases are exacerbated in people with weakened immune systems and spreads with long-term antibiotic treatment. One of these risk factors is oral candidiasis mainly due to Candida albicans. Oral candidiasis can spread if left untreated. Since it is resistant to fluconazole, it may cause esophageal or systematic involvement, diffusion in the blood and eventually, death of the patient [21,22]. Weakened immune systems are much more likely to be infected because they are not strong enough to defend, against virus attack. Hyperactive immunity is also much more dangerous due to cytokine storms and more severe symptoms [23]. Although COVID-19 has not been specifically treated, antibiotic and antiviral prescription along with respiratory care and other supportive care is recommended for crisis management [24].

COVID-19 disease remains a major problem for the world's health care systems, and because of the weakened immune status of patients, reinfection may be associated with varying severities and forms, including the simultaneous occurrence of fungal diseases, and on the other hand, studies in this field in Golestan province, one of the northern provinces of Iran, have been insignificant, so in this study to identify recurrent infections and fungal infections in patients with COVID-19 patients hospitalized in Baqiyatallah Hospital.

The aim of this study was to evaluate reinfection and fungal infections among 785 patients admitted to Baqiyatallah Hospital in northern Iran using epidemiological questionnaire, clinical trials, RT-PCR (reverse-transcription polymerase chain reaction) and CT scan profiles from the Hospital's Information System (HIS).

Methods

Patient characteristics

In this cross-sectional descriptive study, information of 785 inpatient referrals to Baqiyatallah Hospital in Aliabad City (Golestan Provience, Iran) as a research community was retrieved from the HIS during 20 February–21 July 2020. Ethical approval for the study was granted by the Ethics Committee of Golestan University of Medical Sciences (Approval Code: IR. GUMS. rec. 1399.035). According to the treatment instructions, suspected cases were confirmed by RT-PCR method. Some patients were clinically diagnosed based on their lung imaging features, especially CT enrolled by the census method, and was compared between the improved and deceased groups. The required data were collected using a demographic information questionnaire, including age, gender, clinical symptoms, final outcome (including death or survival), a checklist of laboratory findings, radiological information, type of comorbidity, supportive and pharmacological measures during hospitalization, and information on the patients' discharge time. All cases registered in the hospital had a unique national code, so the study variables were studied without any duplication. All registered information of the referred and hospitalized patients within a certain time were included in the study, and there was no limitation in this regard. Also, owing to the importance of reinfection in the studied patients, they were examined and followed in the desired period.

Oral mucosal lesions in one COVID-19 patient

Out of ten patients suspected of oral candidiasis infections, one patient was positive after candidiasis clinical examination. A 47-year-old male with a history of diabetes (type II) and insulin use, levofloxacin 500 mg, meropenem 1 g, then meropenem 50 mg, allopurinol 100 mg, dextromethorphan syrup, PH: 7.29, HCO3:228, PCO2:48 with 42 days of hospitalization in the ICU, and white discharge in mouth was suspected of candidiasis. Two swabs were taken from his oral plaques and sent to the mycology laboratory. One swab was used for direct examination with KOH (10%), and the other swab was used in subgroup dextrose agar containing chloramphenicol. After microscopic observation of the yeast, first, the germ tube was examined and then cultured in CHROMagar Candida and Corn Meal agar containing tween 80. Candida isolate was identified by morphological characteristics in CHROMagar Candida medium (Chrom, France) and confirmed by PCR Sequencing, ITS (internal transcript spacer) gene region of the ribosomal DNA gene selected for duplication. In the present research, we used the following pair of universal primers: ITS1 (-5-TCCGTA GGT GAA CCT GCG G-3) and ITS-4 (5-TCC TCC GCT TAT TGA TAT GC-3). Then the restriction enzyme (Msp I) was used to digest the amplified fragments. Finally, the production of RFLP (restriction fragment length polymorphism) was verified using agarose gels, electrophoresis and yeast isolate due to differences in the band pattern [6,13].

COVID-19 reinfection

The reinfection was described following positive results of SARS-CoV-2 RT-PCR test in patients who previously confirmed for COVID-19.

Statistical analysis

The obtained data were analyzed using the SPSS16 statistical software. Mean and standard deviation (M ± SD) were reported to describe quantitative variables, and number and percentage were reported for the qualitative variables. Pearson's Chi-squared test and Fisher's exact test were used to examining the relationship between the qualitative variables. Kaplan–Meier curve and log-rank test were employed to compare survival function to death for patients based on gender.

Results

Patient demographics

The information of 785 infected patients was analyzed from 20 February to 21 July with a definitive diagnosis of coronavirus. A significant number of cases were in the age group of 20–40 years (64.8%); the majority of them were males (51.7%) and were hospitalized for a mean of 5 days (SD: 4.8). Also the mean age of the patients was 48.67 years (SD: 15.94). Totally, 23.2% (n = 130) of deaths occurred during the entire study period, with the mean age of 63.62 years (SD: 14.5) and the mean hospitalization duration of 4 days (SD: 4.3). Among the 130 case deaths, 59.7% (SD: 4.64) of the patients had chronic underlying diseases and 226 (40%) had comorbidities. As shown, 9.4% of the patients had diabetes and 22.1% of them had other comorbidities including, hypertension and heart disease (Figure 1). 18% of the patients were admitted to the intensive care unit (ICU) and 40.2% of them had no clinical symptoms (74.7%). The most common ethnicity of the patients was Fars (n = 419, 74.7%). The prevalence of the disease in both genders based on ethnicity was not statistically significant (Fisher's exact test, p-value = 0.66).

Figure 1. . Underlying diseases in COVID-19 patients.

Figure 1. 

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Clinical findings

Out of the 561 hospitalized patients whose disease (COVID-19) was confirmed by laboratory tests, RT-PCR or radiography, 197 patients underwent lung CT scan, 26% (n = 52) had unilateral involvement and 21% (n = 42) had bilateral involvement, whereas 3% (n = 6) had normal CT scans Table 1.

Table 1. . CT scan pattern RT-PCR result cross tabulation.

CT scan pattern RT-PCR result Total
  Positive negative  
Unilateral infiltration 9 20 29
28.1% 24.7% 25.7%
Bilateral infiltration 10 20 30
31.3% 24.7% 26.5%
Ground glass 0 5 5
0.0% 6.2% 4.4%
Normal 3 19 22
9.3% 23.4% 32.7%
Unknown 10 17 27
31.3% 21.0% 23.9%
Total 32 81 113
100.0% 100.0% 100.0%
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p-value was less than 0.05 was considered to indicate a statistically significant difference.

Most of the patients were treated with supportive care, including administrating oxygen within hydroxychloroquine (1.1%), hydroxychloroquine and kaletra (28.3%), hydroxychloroquine, and Tamiflu (12.3%), and other antibiotic and antiviral agents (25.3%). The most common antibiotics used for inpatients were vancomycin (10.85%), tavanex (10.32%), azithromycin (8.36%) and meropenem (4/62 %).

Regarding the chart, the survival time to death in patients calculated based on gender during hospitalization showed that the median was 23.25 days (SD: 2.8) (log-rank test) (Figure 2).

Figure 2. . Median survival time until death in COVID-19 patients.

Figure 2. 

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Laboratory findings

Specifically, 398 (71%) out of the 561 patients admitted had positive serological tests, and out of the 337 RT-PCR tests performed, 12.1% had viral RNA detected and 30.8% had a negative result. The laboratory findings showed, that 10.8 and 21/2% of the patients (n = 561) had a decreased and increased lymphocyte count, respectively. Of the 234 patients who were evaluated for ESR (erythrocyte sedimentation rate), 41.71% had increased ESR and 83.42% of the 468 patients whose CRP (C-reactive protein) was measured had high CRP. Therefore, fluctuation in lymphocyte count and increase in CRP were the most sensitive parameters in the patients. According to the results of Mann–Whitney's test, the mean of WBC in the deceased patients was significantly higher than that of the recovered patients.

Baseline demographic characteristics and laboratory information are compared in three general groups of hospitalized patients, patients in ICU/CCU, and deaths in Table 2.

Table 2. . Laboratory and demographic parameters of covid-19 patients.

Mean (std. deviation)
All patients (n = 561) ICU/CCU (n = 101) Deaths (n = 130)
Age (mean ± SD) 57.58 ± 16.9 63.62 ± 14.5 57.69 ± 16.96
Sex, n (%)
Male
Female
304 (54.2%)
257 (45.8%)
58 (19.1%)
43 (16.7%)
71 (54.6%)
59 (45.4%)
SPO2, n (%)
<93
>93
237 (42.2%)
324 (57.8%)
44 (43.6%)
57 (56.4%)
36 (27.7)
94 (72.3%)
Laboratory parameters:mean (SD)
FBS 172.3 (SD: 99.8) 173.2 (SD: 96.6) 209.5 (SD: 119.1)
Lymphocytes 22.4 (SD: 13.52) 19.8 (SD: 10.7) 19.04 (SD: 16.23)
ESR 43.11 (SD: 27.5) 43 (SD: 10.7) 52.49 (SD: 30.36)
CRP, n (%)
Weakly positive
1+
2+
3+
Negative
165 (29.4%)
75 (13.4%)
84 (15%)
74 (13.2%)
163 (29.1%)
27 (26.7%)
19 (18.8%)
17 (16.8%)
14 (13.9%)
24 (23.8)
42 (32.3%)
16 (12.3%)
20 (15.4%)
10 (7.7%)
42 (33.3)
SGOT 65.53 (SD: 195) 110.6 (SD: 380) 102.3 (SD: 189.3)
SGPT 48 (SD: 116.9) 78 (SD: 234) 74.6 (SD: 182.7)
ALP 16608 (SD: 126952) 29243 (SD: 168950) 23850 (SD: 152427.4)
CPK.1 558 (SD: 1205) 355.9 (SD: 575.7) 296 (SD: 639.6)
LDH.1 652.3 (SD: 589) 629 (SD: 335) 1036 (SD: 932)
LDH.2 660.8 (SD: 589.6) 1061 (SD: 906) 988.7 (SD: 797.7)
Urea.1 43 (SD: 34.8) 40 (SD: 24) 55.3 (SD: 41.7)
Urea.2 48.6 (SD: 49) 50 (SD: 27) 60.1 (SD: 44.5)
Creat 1.7 (SD: 4.8) 1.6 (SD: 1.1) 1.8 (SD: 1.2)
WBC 48.3 (SD: 856) 220 (SD: 1931) 10.7 (SD: 6.9)
Plt 232 (SD: 179) 221 (SD: 84) 226 (SD: 100.4)
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LDH: Lactate dehydrogenase; WBC: White blood cell.

Confirmed diagnosis of oral mucosal lesions

A 47-year-old man (with a history of diabetes) was admitted to the CCU. His initial symptoms were acute respiratory problems, and the infection was confirmed by chest computed tomography (CT) and RT-PCR. After 42 days in the hospital, the patient had symptoms such as white spots and redness and inflammation in the oral mucosa. He was administrated to the use 30 units of novorapid insulin, levofloxacin 500 mg, meropenem 1 g, He was administered with meropenem 50 mg, allopurinol 100 mg, dextromethorphan syrup, (PH: 7.29, HCO3: 228, PCO2: 48). Two swabs were taken from the patient's oral plaques and sent to the mycology laboratory. One swab was used for direct examination with 10% KOH and the other swab was cultured in subrodextrose agar containing chloramphenicol. After microscopic observing the yeast, the first germ tube was examined and then cultured in CHROMagar Candida and corn meal agar containing tween 80. The result of the germ tube test was twice as that of large as the mother cell, Also production of chlamydiaconidia was observed in cornmeal agar medium and light green was seen in CHROMagar Candida medium. The fungal infection was diagnosed as Candida albicans. Candida albicans discharge of the patient's oral mucosa candidiasis was detected by phenotypic and genotypic methods. The clinical samples of Candida produced bands with an approximate length of 535 bp (Figure 3). Digestion of the ITS region of Candida albicans using MSP1 enzyme produced two bands of 297 and 338 bp. Candida albicans ATCC 10231 standard was used to confirm the Candida species.

Figure 3. . RFLP-PCR Candida albicans.

Figure 3. 

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SARS-CoV-2 reinfection confirmed diagnosis of reinfection

In a case report, 63 days (∼2 months) after the first visit and hospitalization, a 68-year-old male in patient with a history of different diseases (diabetes, hypertension, asthma, hyperlipidemia and heart disease) presented with respiratory distress and cough symptoms and was admitted to the ICU for 7 days with bilateral involvement in the lungs (Figure 4A), CRP-positive, WBC = 10.2 and SPO2 >93. In the second visit, he was hospitalized for 12 days in the ICU with the symptoms of cough, respiratory distress, bilateral involvement in the lungs (Figure 4B) a positive RT-PCR (CT = 25), WBC = 7, and SPO2 <93. Finally, the patient was recovered and discharged.

Figure 4. . CT-scan in patients.

Figure 4. 

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(A) CT-scan in initial infection patient. (B) CT-scan in re-infection patient.

Discussion

This cross-sectional study was done on 785 patients from 20 February to 21 July 2020 in Golestan province, Iran. The analyzed data and its exacerbating factors showed the essential effect of epidemiological factors for the occurrence and spread of COVID-19 disease.

Various studies have shown that the laboratory data such as CBC and CRP can be useful indicators for predicting COVID-19 [25,26]. Information obtained from these variables can help for diagnosis, treatment [27] and prevent further spread of the disease. Therefore, identifying clinical predictors to determine the likelihood of COVID-19 infection in high-risk groups will be useful [25,26]. The results of a study conducted by Sun et al. on 116 patients to examine peripheral blood disorders showed that the patients with COVID-19 had a decrease in lymphocytes, leukocytes, platelets, and hemoglobin and an increase in neutrophils compared with the healthy individuals. In the ICU group, a decrease in lymphocytes and an increase of neutrophils were observed [28]. Our laboratory findings in line with other studies showed that 10.8 and 21/2% of the patients had a decreased and increased lymphocyte count, respectively, and only 1.92% of them had platelet depletion. Accordingly, it can be concluded that COVID-19 has significant effects on the hematopoietic system, which is often associated with leukopenia and lymphopenia. Hence, undoubtedly, the evaluation of these factors in all clinical stages helps to the care of high-risk persons [29].

Zhoa et al. examined the clinical findings of COVID-19 patients such as age, sex, underlying disease, vital signs and outcome. In addition, laboratory findings were obtained from 91 patients. The results showed that 6.51% of the patients had lymphopenia, 40.7% had an increase in CRP, and 9.8% of them died [30]. Similar to other studies, our results also demonstrated no statistically significant difference in the distribution of mortality ratio by gender (p > 0.05, Chi-square test). Also 71% of the hospitalized patients had an increase in CRP. The highest mortality rate was observed in the elderly and men (51.7%).

In a case–control study, Corchuelo and Ulloa reported a patient who was hospitalized with COVID-19, AML, and diabetes. After hospitalization, the possibility of oral candidiasis was diagnosed with the appearance of lesions in the oral mucosa, which led to the administration of antifungal drugs [21], Salehi et al. studies a total of 53 patients with OPC and reported that Candida albicans (70.7%) was the most common fungi, followed by Candida glabrata (10.7%), Candida dubliniensis (9.2%), Candida parapsilosis (4.6%), Candida tropicalis (3%) and Candida krusei (1.5%) [17]. For a patient with concomitant diabetes and COVID-19, positive Candida culture was isolated from an oral sample, which led to the prescription of caspofungin drugs. This is in line with the results of other studies.

Duggan et al. reported a case of COVID-19 patients who relapsed after complete recovery in 2020. They were elderly and had underlying diseases such as diabetes and Parkinson's disease with symptoms of fever and shortness of breath, and the infection was confirmed by molecular testing and radiography [31]. Also Zhou et al. found that COVID-19 patients who ‘recur’ after discharge are usually older, have poor immune function and have more diseases [32]. Similarly, we observed a case of re-infection in a 68-year-old male patient with underlying diseases such as diabetes, which was confirmed by the laboratory, molecular and CT scan results. Studies showed that both age and primary disease may be associated with exacerbation and recurrence. Re-infection may also affect the onset of the epidemic, WHO report shows that the elderly and those with a history of major medical conditions like diabetes and cardiovascular problems are more likely to develop COVID-19 [33]. The treatment of individuals having diabetes and viral infection will be more difficult because of fluctuations in blood glucose levels, inhibition of interferon-type 1 production, and possible complications of diabetes [15,16]. It seems that patients with heart diseases are much more likely to develop COVID-19. In a study of 1527 patients in China, the prevalence of diabetes, cardiovascular diseases (CVDs), and hypertension were 9.7, 16.4 and 17.1%, respectively [34]. Among the 785 patients in our study, the incidence of diabetes was 9.4%, hypertension 7.5%, heart diseases 3.6%, and other diseases 22.1%. Simultaneous incidence of diabetes and hypertension was 7.7%, and that of diabetes and heart diseases was 3.4%.

The results suggest that the gastrointestinal symptoms caused by this disease are due to the binding of the virus to the angiotensin-converting enzyme receptors, which leads to overexpression of the virus [31]. In the present study, only 8.9% of the hospitalized patients had symptoms like diarrhea, nausea and vomiting, this finding is similar to the results reported by Chen et al. and Zhang et al. [35,36].

The most common symptoms in studies include fever, fatigue, dry cough, anorexia, myalgia, dyspnea and sputum. Specifically, high fever, cough and dyspnea should be carefully examined as they indicate ‘severe or critical cases’ [37]. In a study of 178 patients in 2020, Talebi and colleagues concluded that 52.8% were women, the mean age was 57.1 ± 18 years, 85.4% recovered and 14% died. Shortness of breath (72.5%) followed by cough (61.8%) and fever (48.9%) was the most common symptom. 43.8% of all patients and 71.9% of the deceased patients had at least one underlying disease. There were significant differences in terms of cough in the recovered cases and decreased level of consciousness in the deceased patients (p < 0.05) [38]. Contrarily, men (51.7%) were predominant in our study, and their mean age was 48.67 years (SD: 15.94). Also 7.8% of all patients had no clinical signs and symptoms, while 10.3% of them had respiratory distress, 6.4% had cough, 9.4% showed fever and cough together and 8.4% reported cough and respiratory distress simultaneously. There were significant differences in terms of cough in the recovered cases. However, owing to the behavioral complexities and diverse target sites of COVID-19 in the human body, the complications and symptoms of the disease are unpredictable [39].

It is natural that despite the only case of reinfection reported in our study, recurrence of the disease is underestimated. Also, by confirmatory tests such as serological tests, antibody titers and genomic sequences in more patients, the cause of viral recurrence and the occurrence of fungal diseases can be reported with more confidence.

Conclusion

During this period, re-infection and oral candidiasis were diagnosed in one 68-year-old and another 47-year-old men after 63 and 42 days of initial infection, respectively. Therefore, the important points of this study include: coronavirus reinfection and development of fungal infections in the hospitalized patients. In this study, the patients in the age range of 20–40 years had elevated LDH, lymphocytopenia, thrombocytopenia, fever and cough.

The limitation of our study was the evaluation of coronavirus recurrence and fungal infections in very short period of time in the hospitalized patient. On the other hand, few studies have been contacted to evaluate these problems in COVID-19 patients suffering from underlying diseases. Nowadays, with the increase in the transmission of delta coronavirus in patients taking corticosteroids and antibiotics, and having uncontrolled sugar, organ transplants, etc., we observe an increase in fungal infections such as mucormycosis, which is the cause of death in patients with COVID-19. Therefore, it is recommended to conduct such studies on the importance of controlling underlying diseases as a risk factor for preventing death in patients with COVID-19. The limitation of our study was the evaluation of recurrence and fungal infections referred to the hospital in small time efficiencies.

Summary points.

  • During this period, reinfection and oral candidiasis were diagnosed in a 68-year-old and another 47-year-old man after 63 and 42 days of the initial infection, respectively.

  • A total of patients (785 patients), male: 51.7%, women: 48.3%; age range, 20–40 years were infected.

  • The most common symptoms were fever, cough and lymphocytopenia, thrombocytopenia, elevated LDH, and hypoxia that identified. According to the reports of reinfection, Exposure to COVID-19 may not establish long-term protective immunity to all patients and may predispose them to reinfection.

  • As observed from the beginning of the study to the end of our study (20 February–21 July 2020), few studies were performed to evaluate reinfection and fungal infections in patients with underlying diseases admitted to patients with COVID-19.

  • While today, with the increase in the transmission of delta corona virus in patients taking corticosteroids, antibiotics, uncontrolled sugar, organ transplants, etc., we observe an increase in fungal infection such as mucormycosis causes death in patients with COVID-19.

Acknowledgments

The authors would like to thank Golestan University of Medical Sciences and the laboratory and the nursing team of Baqiyatallah Hospital that are fighting against the illness.

Footnotes

Author contributions

SS Hosseini conceptualized and designed the study. M Naderi, AT Rad, SA Soltani and S Sodagar collected data. Z Mehrbakhsh analyzed the collected data. M Naderi, SS Hosseini and A Tahamtan drafted the manuscript. All authors evaluated and edited the manuscript. All authors have read and approved the final manuscript.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The current study was extracted from a research protocol approved by (11588) University of Medical Sciences, Gorgan, Iran of Ethics Committee (approval code: IR. GUMS. rec. 1399.035). The volunteer who had oral candidiasis gave written consent. The rest of the files were read from the HIS system of the hospital and the patients' files were obtained with the permission of the Ethics Committee of (approval code: IR. GUMS. rec. 1399.035) University of Medical Sciences with the code (11588). This article does not contain any studies with animals performed by any of the authors.

References

  • 1.Segars J, Katler Q, McQueen BD et al. Prior and novel coronaviruses, coronavirus disease 2019 (COVID-19), and human reproduction: what is known? Fertil. Steril. 113(6), 1140–1149 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Mehraeen E, Seyed Alinaghi SA, Nowroozi A et al. A systematic review of ECG findings in patients with COVID-19. Indian Heart J. 72(6), 500–507 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Mehraeen E, Karimi A, Barzegary A et al. Predictors of mortality in patients with COVID-19-a systematic review. Eur. J. Integr. Med. 40, 101226 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Zare F, Teimouri M, Khosravi A et al. COVID-19 re-infection in Shahroud, Iran: a follow-up study. Epidemiol. Infect. 149, e159 (2021). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Falahi S, Kenarkoohi A. COVID-19 reinfection: prolonged shedding or true reinfection? NMNI 38, 100812 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.SeyedAlinaghi S, Oliaei S, Kianzad S et al. Reinfection risk of novel coronavirus (COVID-19): a systematic review of current evidence. World J. Virol. 9(5), 79–90 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Leung Wai K, Ka-fai To, Chan Paul KS et al. Enteric involvement of severe acute respiratory syndrome-associated coronavirus infection. J Gastroenterol. 125, 1011–1017 (2003). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.WHO Coronavirus disease 2019 (COVID-19) situation (2020). https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports
  • 9.Shi Heshui, Han Xiaoyu, Jiang Nanchuan et al. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect. Dis. 20, 425–34 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Tavakoli A, Vahdat K, Keshavarz M. Novel coronavirus disease 2019 (COVID-19): an emerging infectious disease in the 21st Century. Iran South Med. J. 22(6), 432–450 (2020). [Google Scholar]
  • 11.Favalli EG, Ingegnoli F, De Lucia O, Cincinelli G, Cimaz R, Caporali R. COVID-19 infection and rheumatoid arthritis: faraway, so close! Autoimmun Rev. 19(5), 102523 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Pan L, Mu M, Yang P et al. Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: a descriptive, cross-sectional, multicenter study Am. J Gastroenterol. 115(5), 766–773 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Mehraeen E, Behnezhad F, Salehi MA, Noori T, Harandi H, SeyedAlinaghi S. Olfactory and gustatory dysfunctions due to the coronavirus disease (COVID-19): a review of current evidence. Eur Arch Otorhinolaryngol. 278(2), 307–312 (2021). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Zhao M, Wang M, Zhang J et al. Advances in the relationship between coronavirus infection and cardiovascular diseases. Biomed. Pharmacother. 127, 110230 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Pal R, Banerjee M. Are people with uncontrolled diabetes mellitus at high risk of reinfections with COVID-19? Prim. Care Diab. 15(1), 18–20 (2021). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Indini A, Rijavec E, Ghidini M et al. Coronavirus infection and immune system: an insight of COVID-19 in cancer patients. Crit. Rev. Oncol. Hematol. 153, 103059 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Liang W, Guan W, Chen R et al. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Lancet Oncol. 21(3), 335–337 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Dai M, Liu D, Liu M et al. Patients with cancer appear more vulnerable to SARS-COV-2: a multicenter study during the COVID-19 outbreak. Cancer Discov. 10(6), 783–791 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.CDC. Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19) (2020). https://stacks.cdc.gov/view/cdc/89980
  • 20.McClain MT, Park LP, Nicholson B et al. Longitudinal analysis of leukocyte differentials in peripheral blood of patients with acute respiratory viral infections. J. Clin. Virol. 58(4), 689–95 (2013). [DOI] [PubMed] [Google Scholar]
  • 21.Sun S, Cai X, Wang H et al. Abnormalities of peripheral blood system in patients with COVID-19 in Wenzhou, China. Clin. Chim. Acta. 507, 174–180 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Soltani S, Mahmoudi M, Farhadi E. Hematology findings in patients with Coronavirus disease 2019 (COVID-19). IJBIO. 4(7), 303–309 (2020). [Google Scholar]
  • 23.Xiaoqing L, Zhang Run, He Guangsheng. Hematological findings in coronavirus disease 2019: indications of progression of disease. Ann. Hematol. 99, 1421–1428 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Salehi M, Ahmadikia K, Mahmoudi S, Kalantari S, Jamalimoghadamsiahkali S, Izadi A. Mycoses 63(8), 771–778 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Zhao XY, Xu XX, Yin HS et al. Clinical characteristics of patients with 2019 coronavirus disease in a non-Wuhan area of Hubei Province, China: a retrospective study. BMC Infect Dis. 20(1), 311 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Duggan NM, Ludy SM, Shannon BC et al. Is novel coronavirus 2019 reinfection possible? Interpreting dynamic SARS-CoV-2 test results. Am. J. Emerg. Med. 39, 256.e1–256.e3 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Shakerian N, Mofateh R, Saghazadeh A et al. Potential prophylactic and therapeutic effects of respiratory physiotherapy for COVID-19. Acta Biomed. 92(1), e2021020 (2021). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Fisher M. Cardiovascular disease and cardiovascular outcomes in COVID-19. Pract. Diabetes 37(5), 191–193 (2020). [Google Scholar]
  • 29.Bansal M. Cardiovascular disease and COVID-19. Diabetes Metab Syndr. 14(3), 247–250 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Zhang H, Liao YS, Gong J, Liu J, Xia X, Zhang H. Clinical characteristics of coronavirus disease (COVID-19) patients with gastrointestinal symptoms: a report of 164 cases. Dig Liver Dis. 52(10), 1076–1079 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Chen A, Agarwal A, Ravindran N, To C, Zhang T, Thuluvath PJ. Is gastrointestinal symptoms specific for COVID-19 infection? A prospective case-control study from the United States. Gastroenterology 159(3), 1161–1163.e2 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Komurcuoglu B. Clinical and laboratory findings of COVID-19. Eurasian J. Pulmonol. 22(4), 16–18 (2020). [Google Scholar]
  • 33.Zhou L, Liu K, Liu HG. Cause analysis and treatment strategies of “recurrence” with novel coronavirus pneumonia (COVID-19) patients after discharge from hospital. Tuberc Respir Dis. 43(4), 281–284 (2020). [DOI] [PubMed] [Google Scholar]
  • 34.Fisher M. Cardiovascular disease and cardiovascular outcomes in COVID-19. Pract. Diabetes 37(5), 191–193 (2020). [Google Scholar]
  • 35.Bansal M. Cardiovascular disease and COVID-19. Diabetes Metab Syndr. 14(3), 247–250 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Zhang H, Liao Y.S, Gong J, Liu J, Xia X, Zhang H. Clinical characteristics of coronavirus disease (COVID-19) patients with gastrointestinal symptoms: A report of 164 cases. Dig Liver Dis. 52(10), 1076–1079 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Chen A, Agarwal A, Ravindran N, To C, Zhang T, Thuluvath PJ. Is Gastrointestinal symptoms specific for COVID-19 infection? A prospective case-control study from the United States. Gastroenterology 159(3), 1161–1163.e2 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Komurcuoglu B. Clinical and laboratory findings of COVID-19. Eurasian J. Pulmonol. 22(4), 16–18 (2020). [Google Scholar]
  • 39.Talebi Sh, Nematshahi M, Tajabadi A, Khosrojerdi A. Comparison of clinical and epidemiological characteristics of deceased and recovered patients with COVID-19 in Sabzevar, Iran. Mil. 22(6), 509–516 (2020). [Google Scholar]

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