A comparative study of the laboratory features of COVID‐19 and other viral pneumonias in the recovery stage

Abstract Background Clinical recovery does not mean full recovery. It is necessary to explore the aftereffects of COVID‐19 in patients and compare the laboratory features of COVID‐19 and other viral pneumonias in the recovery stages. Methods Forty‐seven cases of COVID‐19 and 45 cases of other viral pneumonias (control) were included in this study. The laboratory parameters were compared between COVID‐19 and control patients as well as severe and moderate COVID‐19 patients from the clinical recovery stage to the 4 weeks postdischarge recovery stage. Results A higher RDW‐CV level and neutrophil percentage and lower levels of total proteins, lymphocytes, eosinophils, and MCH were found in COVID‐19 patients compared with those in controls from the clinical recovery to the postdischarge recovery stages. Further analysis showed that decreases in lymphocytes, total proteins, and SOD and elevations in neutrophils, FDP, CRP, and ESR were more common in severe than moderate cases of COVID‐19 during hospitalization; however, differences in these indicators, except total proteins, were not observed in the postdischarge recovery stages. Additionally, only 76.9% of COVID‐19 patients were positive for IgG antibodies against SARS‐CoV‐2 in the convalescence stage, and one patient that was negative for specific IgG was reinfected. Conclusions This study demonstrated that patients recovering from COVID‐19 might need better care than that patients with other viral pneumonias due to the possibility of having poor immunity and nutritional conditions. These findings provide new insights to improve the understanding of COVID‐19 and improve care for patients affected by these kinds of pandemics in the future.


| INTRODUC TI ON
A novel coronavirus (SARS-CoV-2) is the etiological agent responsible for the ongoing pandemic of coronavirus disease 2019 (COVID- 19). The genome of the virus, which belongs to lineage B of the betacoronavirus genus, has nearly 80% similarity to the genome of the severe acute respiratory syndrome coronavirus (SARS-CoV). 1,2 Infection with SARS-CoV-2 is more likely to affect older men with chronic illnesses and could result in acute respiratory distress syndrome (ARDS). 3 Moreover, lymphopenia and inflammatory cytokine storms could be associated with disease severity and fatal outcomes. 4 As of May 20, 2020, 4,947,929 cases have been confirmed worldwide, and 324,776 patients have died. Fortunately, more than 1.7 million people around the world are known to have already been discharged from the hospital, according to data from Johns Hopkins University. However, clinical recovery does not necessarily mean full recovery; some COVID-19 patients still have a mild cough and feel tired even once they are considered recovered and are no longer contagious, and usually, it takes a long time for patients to feel fully normal. 5 There are still many uncertainties regarding recovered patients with COVID-19: How does the illness affect them in the long run, and what are the different features that distinguish COVID-19 and other infectious diseases in the recovery stages? It is noteworthy that other viral pneumonias share similar epidemiological characteristics and clinical manifestations with COVID-19 and occur in the same seasons. 6 Currently, several studies have compared the differences in epidemiology, clinical manifestations, and laboratory characteristics between SARS-CoV-2-positive and SARS-CoV-2negative patients on admission. As reported, urea, creatinine, and procalcitonin were important features discriminating COVID-19 from SARS-CoV-2-negative patients. 7 Additionally, COVID-19 patients were more likely to exhibit a nonproductive cough, fatigue, gastrointestinal symptoms, and ground-glass opacities than H1N1 patients. 8 However, few reports have focused on the characteristics of COVID-19 patients after discharge upon follow-up, and the differences between COVID-19 and other viral pneumonias in the recovery stages remain to be elucidated. In this study, a systematic review and pooled analysis were performed to compare the laboratory characteristics of COVID-19 patients and patients with other viral pneumonias from the clinical recovery stage to the 4 weeks postdischarge recovery stage. It is hoped that these findings will provide additional useful and supplementary information for understanding COVID-19 and for improving therapies and care for patients in similar kinds of pandemics in the future.

| Data collection
Demographic features, clinical symptoms, and laboratory results were obtained from electronic medical records. Usually, the median time from onset to clinical recovery for mild cases is approximately 2 weeks and is 3-6 weeks for patients with severe disease.
COVID-19 patients in clinical recovery should meet the following criteria: normal body temperature for more than three days, two negative RT-PCR tests of respiratory specimens at 24-hour intervals, and a chest CT (computed tomography) showing that the lesion is essentially absorbed or that only a few fibrous stripes can be observed. The laboratory results, including hematological and biochemical data, were collected at the time of admission and at different recovery stages. In broad terms, the recovery stages included the clinical recovery stage (1-3 days before discharge) and the postdischarge recovery stages (2-and 4-week follow-up visits).
The collected data were independently reviewed and checked by two reviewers.

| Laboratory measurements
Real-time reverse transcription-polymerase chain reaction (rRT-PCR) was used for the SARS-CoV-2 nucleic acid test. Briefly, throat swab samples were collected for extracting viral RNA from patients. Then, the rRT-PCR assay was performed using a SARS-CoV-2 nucleic acid detection kit according to the manufacturer's protocol (ShengXiang Biotech Co Ltd). The IgM and IgG antibodies against SARS-CoV-2 in serum samples were tested using colloidal gold immunochromatography assay kits supplied by Lizhu Reagent Co., Ltd. A PNEUMOSLIDE kit (Vircell) was employed to detect IgM antibodies against 9 common respiratory pathogens, includ- and ADVIA 2400 automatic chemical analyzer (Bayer) were used to analyze routine blood and biochemical parameters, respectively. Evaluation of blood coagulation was performed by an ACL TOP 700 (Werfen). All laboratory parameters were obtained via

| Statistical analysis
All laboratory statistical data are presented as the mean ± SEM; age and number of days are described as the median (interquartile range values, IQR), and categorical variables are described as the number (percentage). Independent group t tests or Mann-Whitney tests were used to compare means. Chi-squared and Fisher's exact tests were used to compare proportions for categorical variables. Twosided comparisons with a p value less than 0.05 were considered significant. The data were analyzed using SPSS 16 (Chicago, USA) and GraphPad Prism 8.0.

TA B L E 1 Clinical baseline characteristics of COVID-19 patients and control cases at admission
Note: P < .05 was considered statistically significant.
Abbreviation: IQR, interquartile range. patients (42 years) but without a significant difference. Meanwhile, no obvious differences were found in terms of the gender distribution or major clinical manifestations between the two groups, except that diarrhea was more common and expectoration was less common in COVID-19 patients. On the other hand, the severe COVID-19 group had more patients with high fever (>39℃) and an older median age (62 years vs 48 years) compared with the moderate group (P < .05).
The major differences in laboratory findings between COVID-19 and control patients at admission are shown in Table 2. Higher values for the red blood cell distribution width-correlation variance

| Differences in laboratory parameters in severe and moderate COVID-19 patients in the recovery stages
To further investigate the effect of the severity of COVID-19 in the recovery stages, the dynamic laboratory parameters in severe and moderate COVID-19 patients were compared as well. At the clinical recovery stage, severe patients with COVID-19 had lower levels of total proteins (P < .05), albumin (P < .01), superoxide dismutase (SOD, P < .01), and lymphocytes (P < .01); higher levels of neutrophils (P < .05), C-reactive protein (CRP, P < .01), and fibrinogen degradation products (FDP, P < .05); and a higher erythrocyte sedimentation rate (ESR, P < .01) than moderate patients (Table 3)

AUTH O R CO NTR I B UTI O N S
MY designed the study and drafted the article. GLZ and YYS collected and analyzed the data. XLC and XWT reviewed the data. XMS and LJZ contributed to the statistical analysis. LYD took responsibility for obtaining ethical approval. HRW and YYS revised the article.