Relationship between Training Load Management and Immunoglobulin A to Avoid Immunosuppression after Soccer Training and Competition: A Theoretical Framework Based on COVID-19 for Athletes’ Healthcare

Immunoglobulin A (IgA), which is the main effector against upper respiratory tract viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been related to training load management. The aim of this systematic review was to establish the relationship between training load and salivary IgA based on current evidence in order to avoid immunosuppression after exercise and players´ vulnerability to virus contagion. A systematic review of relevant articles was carried out using two electronic databases (PubMed and Web of Science) until 19 May 2021. From a total of 127 studies initially found, 23 were included in the qualitative synthesis. These studies were clustered depending on stress level. The salivary IgA was analysed considering soccer-specific treadmill exercise and repeated sprint drills (n = 5), matches (n = 7), and during certain periods during the season or pre-season (n = 11). Repeated sprint ability tests and treadmill exercises are suitable exercises for the first steps on return to play periods yet still maintain social distance. A rest or moderate training sessions (technical/tactical) are suggested after official matches to ensure 16–18 h to recover IgA levels, while periods with multiple matches per week with limited recovery time should be avoided. Weekly training load should assume a small increment (<10%) to ensure IgA immune responses, especially, during the post coronavirus disease 2019 (COVID-19) season.


Introduction
In soccer, the quantification of training load is crucial to ensure players' optimal performance, and to reduce injury occurrences [1]. Its quantification may be carried out through electronic performance and tracking systems or inertial devices, with additional technologies such as heart-rate devices, or using other strategies such as blood analyses or salivary tests. Each reports different information about players' performance, and although some studies found a statistical relationship between them [2,3], it needs further research. Therefore, with the aim to detect issues related to biomarkers, blood or salivary test are needed. Among them, saliva samples, which make available hormone levels (e.g., testosterone and/or cortisol) and antibodies (e.g., immunoglobulin A), seem to be growing in popularity [4]. AND (immunity OR "Immunoglobulin A" OR sIgA OR "sIgA secretion rate" OR "srIgA" OR "mucosal immunity" OR "upper respiratory symptom *" OR URS). Due to the high number of articles found, the present systematic review summarized all articles performed in soccer, while the PART I was focused on the remaining team sports (rugby, Australian football, basketball, handball, ice hockey, futsal) [20].

Screening Strategy and Study Selection
After completion of the search, results were compared between researchers to ensure the same number of articles was found. Then, one of the authors (MR) downloaded the main data from the articles (title, authors, date, and database) to an Excel spread sheet (Microsoft Excel, Microsoft, Redmond, WA, USA) and removed duplicate records. Subsequently, the same authors screened the remaining records to verify the inclusion/exclusion criteria using a hierarchical approach in two phases. The papers were excluded when they met the following exclusion criteria: (1) articles not considered soccer athletes; (2) not salivary related interventions; and (3) biomarkers non-related with immunology (IgA); (4) articles that assessed the influence of another factor (e.g., nutritional intervention) in IgA response, or the effects of IgA in another contexts (e.g., oral health); (5) non-original research papers (i.e., systematic reviews, conferences or meetings).

Data Analysis
Each article was classified depending on the type of stressor: (1) soccer-specific treadmill and repeated sprint drills, (2) matches and, (3) season periods (any period during the season or pre-season that contains only training sessions or training sessions and matches). Each reference was detailed based on the following: sample, stressor factor and its characteristics, sIgA test moment and outcomes, relationship with URTI, and concluding remarks and lessons learned. The specifications about them were provided when the data of several studies were provided in the discussion and conclusions.

Identification and Selection of Studies
A total of 127 (PubMed = 49; Web of Sciences = 78) documents were initially retrieved from the databases, of which 47 were duplicated. Thus, a total of 80 articles were downloaded. After screening the titles and abstracts against criteria 1 (where applicable), and the full text of the remaining papers against the same criteria, 38 studies were excluded. From the 42 articles, 2, 5, 8, and 5 were ruled out against criteria 2, 3, 4 and 5, respectively. Additionally, 2 articles were added from external sources. Therefore, 23 studies were included for the qualitative analysis ( Figure 1).
The decrements in sIgA, specially, in matches 2 and 6 Significant correlations were seen between the individual reports of URTI and the decrease in IgA levels in match 2 and 6.
The monitoring of sIgA could provide a useful and noninvasive approach for predicting URTI occurrences.
In fact, decrements in mucosal immunity (IgA concentrations) may lead to a greater incidence of URTI. IgA concentration did not change after any match.
-Salivary cortisol and testosterone concentrations increased especially after the first match of a final, without affecting IgA levels.
It was speculated that increased testosterone concentration in women after football matches may play a protecting role against immune suppression usually observed after intense exercise.       Pre-breakfast 90 min before training session.
Higher scores of sIgA were observed in MD-2 and MD-1, comparing to all others. No differences were found between playing positions with sIgA assessment.
-A short-term preparation for international competition induces detectable perturbations in IgA. Additionally, from 18 articles, nine considered periods with multiple matches per week with limited recovery time as a characteristic of stressor intervention: three of them during soccer-specific protocols [25,27,28], one during season periods [36], and five during consecutive matches [5,9,29,31,32] (Tables 1-3).

Discussion
The aim of this systematic review was to analyze the relationship between training load and sIgA based on current evidence. The main findings were: (1) sIgA is a valid metric to assess immune function of players; (2) repeated sprint ability test and treadmill exercises were not sufficient stressors to induce immune suppression sIgA protein response; (3) although it is not clear the impact of non-official matches and the periods with a unique match per week in IgA, the official matches and periods with multiple matches per week with limited recovery time induced decrements in IgA responses; (4) 18-36 h after a match may be needed to ensure a restart of IgA levels to a pre-match baseline; (5) weekly training load increases should not exceed the 5-10% with respect to the baseline of the previous training sessions; and, (6) IgA might be more responsive to training volume rather than intensity.

Repeated Sprint Ability and Treadmill Exercises
The main findings showed the sIgA test measured before, during, and after repeated sprint ability tests [23] or during treadmill soccer-specific protocols [25][26][27][28] did not compromise sIgA responses. Because soccer performance is sport that combine high-intensity efforts with lower intensities [40], seven 40 m sprints with 25 s rest seem similar to soccerspecific efforts. However, it did not suppress the immune system, likely due to a lack of real competition situations and psychological stressors [5,13,41]. Even intermittent exercise seems to induce lower suppression on IgA response than continuous exercise, even though the same treadmill work-rate was programmed [26]. This is consistent with Figueiredo et al. [2], who found IgA might be more responsive to volume (i.e., training time and distance covered) rather than intensity (distance covered per min, and high-speed running), as was supported by other studies [3]. Additionally, Moreira et al. [30] did not find a significant effect in sIgA even when the volume of the match was reduced. Therefore, this leads us to suggest increases in training volume rather than intensity must be considered with caution to avoid immunological responses from IgA protein.
In addition to the protocol proposed by Rodrigues de Araujo et al. [23], some studies that analyzed saliva sampled after a test showed high correlations with soccer-specific volume/intensity efforts [24]. The protocol was composed of two 45 min periods. Each "half" included seven static pauses (60 s, 30 s, and 15 s), 40 actions of walking (2 at 33 s, 2 at 30 s, 36 at 25 s), 30 jogging bouts (10 at 49 s, 20 at 26 s), 22 bouts cruising (22 at 12 s), and 16 sprints (2 at 9 s and 14 at 8 s). After the first 45 min and a 15 min intermission, the exercise was continued for a further 45 min to correspond to the duration of a soccer game [26]. However, this protocol neither found differences before in none of these scenarios: (1) during (i.e., in a rest time) and after (i.e., immediately, 6 h, 24 h or 48 h) congested fixtured treadmill exercises; (2) with two bouts and 2 h between them [27]; (3) with 2 bouts and 48 h rest between them [28], or, (4) with 3 bouts and 48 h rest between them [25]. Therefore, considering that 18-36 h have been needed to recover IgA levels [30,33,36], and analyzing that no effects in sIgA were found in two treadmill exercise separated by 2 h, strength and conditioning coaches and medical staffs may implement both of these protocols [23,24] on the first steps on return to play period. This suggestion should be followed, at least, when the social distancing is necessary [12,[42][43][44], or during confinement periods. At a practical level, at least the repeated sprint ability test should be performed with no more than five players participating in training sessions at the same time, with 5 m separating the players, and with their own lane for running and sprints. If the requirement cannot be met, the same lane may be used by more players, but they must maintain a distance between each other of at least 40 m when sprinting [12].

Matches during Intensive and Non-Intensive Fixture Schedules
Although some authors did not find IgA decrements after soccer matches [29,34], most authors agree with a decrement in IgA levels (up to 75% from baseline) after soccer matches [5,9,[30][31][32][33], which may induce URTI [5,9]. Thus, training load management may be crucial to avoid virus contagion. In fact, a low level of sIgA is associated with an increased risk of URTI in athletes [9,10], and SARS-CoV-2 [17]. In this sense, strength and conditioning coaches should programme 18-36 h of rest after a match [30,33,36] to ensure a restart of IgA level to a pre-match baseline. These rest days or days with moderate intensity training may be focused on the acquisition of technical/tactical concepts as programmed by Owen et al. [3].
In addition to acute exercise, it is well known that heavy chronic exercise is associated with an increased risk of IgA suppression and URTI [13,30]. In this regard, some studies found a sIgA decrease during periods with multiple matches per week with limited recovery time [9,31,32]. The accumulated fatigue induced by the physiological and psychological stressors imposed by training and competition in a short timeframe might negatively affect their mucosal immunity [9,31,32]. It is clearly a failure to recover fully between sessions was suggested to cause immunosuppression [28], the aforementioned 18-36 h recovery period is recommended [6,30,33,36]. Similarly, Page et al. [25] suggested players possess the capacity to complete two games with <72 h recovery, but that the risk of injury is increased if a third game is completed at this frequency [25]. Subsequently, soccer clubs and federations should be aware of the competition calendar programming as a protective action to minimize players' vulnerability to contact SARS-CoV-2 or other viruses. However, those league competitions in which are often played a unique match per week may be started. As a practical alternative, squad rotation is an option where the playing roster is sufficiently large. Rather than excluding a player from a game to facilitate recovery, a substitution strategy may be more practical given the physical demands. Page et al. [25] found substitutions made no later than the 60 th minute of the match may have a beneficial effect on reducing the fatigue response associated with match-play. It is consistent with Morgans et al. [32] who found an evident declination in sIgA in players that played more than 50% of the total minutes played.

Preparation Periods (Matches/Training or Training) during Intensive and Non-Intensive Fixture Schedules
IgA protein levels tend to decrease during time periods with training, and even more so if these periods include high-intensity sessions [2,34,37], and during the competitive period [8,10,13]. In addition, despite one exception [16], different studies found relationships between IgA and URTI [8][9][10]35]. In fact, Putlur et al. [13] stated 82% of illnesses could be explained by a preceding decrease in sIgA. In practical terms, a decrement of non-common IgA levels could lead to an URTI three days later [35]. This finding enhances sIgA as a useful predictor for URTI.
Depending on the level of the competition and team, soccer players should be prepared to carry out 3-7 training sessions during domestic leagues, or tournament preparations. While some high-level soccer teams often compete twice a week, most young, amateur and the vast majority of professional soccer teams have to play one match a week [1]. A training week (i.e., microcycle) is typically designed to ensure readiness to play in the next official match. Regardless of the competition level and match features, the organization of the weekly training load should warrant peak performance in the most important session of the week: the official match [1]. From studies that analyzed the effects of IgA over four training sessions during the same week (match day -4, -3, -2, -1), the authors found the accumulation of training sessions induce detectable perturbations to mucosal immunity. Thereby it provides objective evidence for the administration of appropriate interventions to prepare players for the physical stress for the game day by self [2,34,37]. Therefore, the aforementioned suggestions about rest or moderate training days should be applicable to each microcycle.
In addition to the combination of rest days, high-intensity and moderate intensity sessions, a weekly training load increment that does not exceed 5-10% from the previous workload should be considered [4,43] during each microcycle. Gleeson [6] indicated moderate exercise can restore optimal antibody responses in the face of stressors. Therefore, strength and conditioning coaches should program a short prophylactic period (i.e., detraining period) after an intense session to attenuate mucosa immunosuppression related to URTI symptoms [8]. In addition, these suggestions should be completed with nutritional (e.g. carbohydrate enrichment diet) [18,44,45], lifestyle (e.g., sleep disturbance) [4,18,44], and other (e.g., adverse environment conditions, international travels, hygiene suggestions) complementary strategies [4].
In summary, since some authors suggested the management of training loads to avoid immunosuppression against the virus (e.g., SARS-CoV-2) contagion, strength and conditioning coaches and sports scientists are called to share information based on real data. In this sense, the present systematic review highlights that moderate (5-10%) increments of weekly volume/intensity training load during domestic leagues and, the periodization of rest and/or moderate training sessions after matches or very high-intensity efforts. In addition, since some authors encourage coaches to program training tasks with social distancing during the first periods of returning to play, repeated sprint ability tests and treadmill soccer-specific exercises may be suitable alternatives. However, they should be completed with additional tasks which address the limitations about non-real situations of these non-contextualized drills. Finally, taking to account the pressures derived from the economy, together with those of social origin, lead to an almost forced start of sports competitions after a period of confinement worldwide [19], the suggestion of suspense the periods with multiple matches per week with limited recovery time from calendars during the post-COVID-19 home-confinement soccer season is be made with caution. However, since older players (>15 years) showed stronger immune responders than young players [10], this suggestion could be followed, at least, in non-professional populations.

Study Limitations
Since economic, social, and health issues must be considered in decisions on competition restart and other federation concerns related to the pandemic, and considering that SARS-CoV-2 propagation depends on a wide range of factors in addition to those mentioned in this systematic review, the authors would only like to make some recommendations and best practices based on current evidence.
These concluding remarks may highlight some recommendations to prevent an athlete's vulnerability to immunosuppression, which may be an important factor in their return to play post COVID-19. Therefore, the relationship between training load and sIgA is evidence, while the relationship between IgA and URTI is not clear. However, the relationship between these stressors and the risk of illness should be further researched. In this regard, the authors encourage practitioners to share daily information on the dynamic of training load during the previous 15-20 days prior to a contagion.

Conclusions
Lessons learned and concluding remarks are six-fold: (1) the salivary IgA test is a valid metric to the control immune function of players, at least, during the initial stages of return to play after the COVID-19 confinement period. (2) The repeated sprint ability test and treadmill exercises are suitable training protocols to perform during periods with social-distancing necessities (e.g., the first steps of return to play) or during confinement.
(3) The impact of non-official matches and periods with a single match per week in IgA is not clear. Therefore, a restart of leagues in which a unique match per week is played, and considering social and economic pressures, may be suitable after the confinement period. However, we suggest a reduction of those competitions which induce a period with multiple matches per week with limited recovery time to avoid immunosuppression after exercise and players vulnerability to virus contagion. (4) To ensure a restart of IgA level to a pre-match baseline, programming 18-36 h after a match formed by a rest day and/or moderate intensity training sessions (i.e., technical/tactical sessions). (5) A progressive increment of weekly training load should be carefully undertaken (increment of 5-10% weekly) to attenuate immunosuppression by IgA protein. Finally, (6) although it is not clear, and further research is necessary to support this affirmation, it could be that sIgA might be more responsive to training volume (e.g., training time, the volume of training, time spent in competition) rather than intensity (distance covered per min, and high-speed running). Moreover, this affirmation should be supported with some of the wide possibilities of variables derived from the current technology.

Future Research
Interestingly, some articles suggested some concluding remarks that should be considered with caution due to the lack of further research. They are summarized in two ways: (1) the relationship between electronic performance and tracking systems, and subjective exertion and wellness questionnaires with IgA levels; and, (2) the relationship between other biomarkers and IgA.
Technology and questionnaires, and IgA: due to the fast training/competition evaluation and prescription that new technologies (i.e., electronic performance and tracking systems) allow, and considering that today there is not a professional soccer club without these essential tools for training load monitoring, future research should associate variables derived from global positioning systems, semi-automatic video camera systems or local positioning systems. This idea was started by authors who found that IgA levels are dependent on some global positioning system variables (total distance variable, accelerations, and total load) [2,3], RPE [3,9,30], and wellness questionnaires [37].
Biomarkers and IgA: since some studies observed soccer athletes with testosterone level decreases less than those for IgA [10,29,33], it was speculated increased testosterone concentration after football matches may play a protecting role against immune suppression usually observed after intense exercise.